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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
CT22-GSOP-RF02 6.0External Data Monitoring Committee and Internal Review Committee Charter Template
01-Nov-2019
Page 1of 34
TMF Doc ID: 64.05 and 713.02
C459
Investigational BNT162 Vaccine Program
PF-07302048
Version: 5.0
Date: 04-Nov-2020
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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
CT22-GSOP-RF02 6.0External Data Monitoring Committee and Internal Review Committee Charter Template
01-Nov-2019
Page 2of 34
TMF Doc ID: 64.05 and 713.02
TABLE OF CONTENTS
APPENDI CES................................ ................................ ................................ ........................... 3
1. INTRODUCTION ................................ ................................ ................................ ................. 5
1.1. Study Design................................ ................................ ................................ .............5
1.2. Purpose of the Committee ................................ ................................ ......................... 5
1.3.Committee Close -Out................................ ................................ ................................ 6
2. COMMI TTEE MEMBERS HIP................................ ................................ ............................. 6
2.1. Conflicts of I nterest................................ ................................ ................................ ...6
2.2. Confidentiality Agreement/Contract ................................ ................................ .........6
2.3. Authorship................................ ................................ ................................ ................. 6
3. ROLES AND RESPONS IBILITIES................................ ................................ ..................... 7
3.1. Committee Members ................................ ................................ ................................ .7
3.2. Committee Chairperson................................ ................................ ............................. 7
3.3. Committee L iaison................................ ................................ ................................ ....7
3.4. Reporti ng Team................................ ................................ ................................ .........8
3.5. Study Team................................ ................................ ................................ ...............9
4. COMMI TTEE MEETING S................................ ................................ ................................ .10
4.1. Meeting Schedule/Frequency ................................ ................................ .................. 10
4.2. Start-up Meeting ................................ ................................ ................................ ......10
4.3. Review Meetings ................................ ................................ ................................ .....11
4.4. Review Meeting Format................................ ................................ .......................... 12
4.4.1. Open Session ................................ ................................ .............................. 12
4.4.2. Closed Session ................................ ................................ ............................ 12
4.5. Voting Procedure ................................ ................................ ................................ .....12
4.6.AD HOC Meetings for Emergent Safet y Data................................ ........................ 13
4.7. Meeting Minutes ................................ ................................ ................................ .....13
5. DATA PROVIDED TO THE COMMITTEE AND PA RAMETERS TO BE
MONITORED/REVIEWED B Y THE COMMITTEE ................................ ....................... 13
5.1. C4591001 Study Only................................ ................................ ............................. 13
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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
CT22-GSOP-RF02 6.0External Data Monitoring Committee and Internal Review Committee Charter Template
01-Nov-2019
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TMF Doc ID: 64.05 and 713.02
5.1.1. Serious Adverse Events ................................ ................................ ..............14
5.1.2. Other Safet y................................ ................................ ................................ 14
5.1.3. Surveillance of Events That Could Represent Enhanced COVID -19
Disease................................ ................................ ................................ .............14
5.1.4. Immunogenicity................................ ................................ .......................... 15
5.1.5. Efficacy ................................ ................................ ................................ .......15
5.2. All Other Stu dies................................ ................................ ................................ .....15
5.2.1. Serious Adverse Events ................................ ................................ ..............15
5.2.2. Other Safet y................................ ................................ ................................ 16
5.2.3. Immunogenicity................................ ................................ .......................... 16
5.2.4. Efficacy ................................ ................................ ................................ .......16
5.3. Provision of Study Data to the Committee ................................ .............................. 16
5.3.1. Open Session Data ................................ ................................ ...................... 16
5.3.2. Closed Session Data................................ ................................ ................... 17
5.4. Database Information ................................ ................................ .............................. 17
6. COMMUNI CATION PL AN BETWEEN THE PFIZER AND THE COMMI TTEE.........18
6.1. Recommendations ................................ ................................ ................................ ...19
6.2. Communication of Recommendations ................................ ................................ ....19
6.3. External Pfizer Communication................................ ................................ ..............19
6.4. Pfizer I nternal Safety Review Committee ................................ ............................... 20
7. WRITTEN RECORDS ................................ ................................ ................................ ........21
7.1. Deliverables to Pfizer ................................ ................................ .............................. 21
7.2. General Project File ................................ ................................ ................................ .21
7.3. Unblinded data in SAS® Datasets ................................ ................................ ..........22
8. CHARTER HI STORY................................ ................................ ................................ .........22
APPENDICES
Appendix 1. Committee Membership Log................................ ................................ ..............23
Appendix 2. Plan to Control Dissemination of Results................................ ........................... 26
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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
CT22-GSOP-RF02 6.0External Data Monitoring Committee and Internal Review Committee Charter Template
01-Nov-2019
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TMF Doc ID: 64.05 and 713.02
Appendix 3. Key Contacts ................................ ................................ ................................ .......27
Appendix 4. List of Studies (if committee is to oversee multiple studies) .............................. 34
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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
CT22-GSOP-RF02 6.0External Data Monitoring Committee and Internal Review Committee Charter Template
01-Nov-2019
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1.INTRODUCTION
This External Data Monitoring Committee ( E-DMC) (hereafter referred to as “the
committee”) is a single, external, independent, expert advisory group established to oversee
safety and efficacy data from theBNT162 Vaccine Program. The primary rationale for
establishing the committee is to make certain that appropriate external safeguards are in place
to help ensure the safet y of subjects and to maintain scientific rigor and study integrity while
the trial is on -going.
Pfizer is responsible for conducting this study . BioNTechis the regulatory sponsor of this
study.
1.1.Study Design
The COVID -19 program is being developed to address thepandemic crisis which has spread
globally at high speed.There are currently no vaccines to prevent infection with
SARS-CoV-2 or antiviral drugs to treat COVID -19.
Given therapid transmission of COVID -19 and incidence of disease in the United States and
elsewhere, the rapid development of a safe andeffective vaccine is of utmost importance.
Inthe COVID -19 vaccine program, the safety and tolerability of the BNT162 vaccine candidates
will be evaluated by assessing prompted local injection -site reactions and systemic events, as
well as adverse events and serious adverse events. Predefined stopping rules may be used to
ensure safety of study subjects and guide dose escalationa nd participants may also undergo
hematological and chemistry evaluation as defined per protocol . These procedures are described
in detail in each study protocol where relevant. The background of the COVID -19 vaccine
candidates and pre-clinical development is described in the BNT162 COVID -19 Investigator
Brochure (IB). The updated IB will be provided to the committee when available.
Please refer to the current study protocolsfor details of the study design.
1.2.Purpose of the Commit tee
The committee will review accumulating safet y dataacross all studies , as well as efficacy
data in the Phase 2/3portion of the C4591001 study . The committee will advise Pfizer
regarding the safet y of current participants and those yet to be recruited, as well as the
continuing scientific validity of the trial . In addition to safet y review b y the committee ,
qualified Pfizerpersonnel will review safet ydata as specified in the safety surveillance
review plan and will inform the committee of significant findings. Efficacy data fromthe
C4591001 study will be available to the committee whenthere is a planned interim analy sis
of efficacy or if this is considered necessary to conduct arisk-benefit assessment.
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EXTERNAL DATA MONITO RING COMMITTEE
PFIZER INTERNAL USE ONLY
The official version of this form is located in the electronic document management system.
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01-Nov-2019
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1.3.Committee Close -Out
The committee will have completed its work and been dissolved whenit has reviewed final
safety data from the last study within the scope of this charter.
2.COMMITTEE MEMBERSHIP
The committee consists of a chairperson and 2-4additional members, as indicated in the list
ofmembers in Appendix 1Committee Membership Log including at least one with medical
qualifications and at least one other who is a statistician.
During the conduct of the study ,membership of the committee may change based on
expertise needed , availability , and new conflicts of interest that warrant a change . A dated
log mustbe maintained in Appendix 1reflecting any changes in membership . Committee
membership is to be for the duration specified in each member’s contract. If any member
leavesthe committee, Pfizerwill promptly appoint areplacement in consultation with the
committee chairperson ,if needed.
2.1.Conflicts of Interest
The committee members will complete a CT22-GSOP-RF01Independent Oversight
Committee Member Conflict of I nterest Form . Committee members should be free of
apparent significant conflicts of interest . Any potential conflict of interest that develops
during a member’s tenure on the committee must be disclosed by the committee member.
Pfizerwill determine if any potential conflict requires termination of committee membership.
Each time the committee meets, the study team will ask the committee members to consider
whether or not an y changes in thei r conflict of interest status have emerged. Status must be
recorded in the committee open meeting minutes and any potential conflicts must be reported
using CT22-GSOP-RF01.
2.2.Confidential ity Agreement/ Contract
A written agreement (i.e., contract, including confidentiality agreement) must be in place for
each external committee member before an y services are rendered. No communication ,
either written or verbal, concerning the deliberations or recommendations of the committee
will be made outside of the committee without approval of Pfizer, except as p rovided for in
this charter (refer to Section 6Communication PlanBetween Pfizer and the Committee ).
2.3.Authorship
A committee member must not be an author of a publication emanating from any study on
the BNT162 vaccine program for which they are a member.
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3.ROLES AND RESPONSIBI LITIES
3.1.Committee Members
The primary responsibilities of the committee members are:
Review, endors e,and implement the charter.
Assess the safet y data from the study on a regular basis ( refer to Section 4.1
Meeting/Schedule Frequency ) throughout the duration of the trial.
Assess efficacy data for efficacy and/or futility during Phase 2/3.
Providean informed risk- benefitassessment and advis e Pfizerregarding the continuation
of the trial based on the reviewed data .
Provide guidance, where appropriate, on additional questions presented b y the study team
prior to reviewmeetings.
Adhereto agreements related to potential conflicts of interest.
3.2.Committee Chairperson
The primary responsibilities of the committee chairperson are:
Review and approvethe charter on behalf of the committee members.
Facilitate discussion by integrating differing points of view and moving the committee
towards recommendations to be provided to Pfizerin a timely fashion.
Prepareclosedsession meeting minutes (or via a designee).
Complete CT22-GSOP-RF11Brief Recommendation Form and submit to the study team,
according to the communication plan (refer to Section 6Communication Plan Between
Pfizerand the Commi ttee).
Communicate with thestudy teamaccording to the communication plan on behalf of the
committee (refer to Section 6Communication Plan Between Pfizer and the Committee ).
Provide all written records to the study teamfor archiving .
3.3.Committee Liaison
The committee liaisonis not a member of the study team for any study being reviewed b y the
committee . The committee liaison is designated by Pfizerand will maintain independence
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01-Nov-2019
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from the study team for the duration of the trial. The primary responsibilities of the
committee liaison are:
Serve as the primary liaison between the committee and Pfizermanagement.
Receive and distribute, according to the communication plan, the committee
recommendations from the committee chairperson.
Ensure the committee has access to timel y information about the study .
Handle and maintain a record of communications between the committee and Pfizer.
Manage written records (e.g., closed session meeting minutes and CT22-GSOP-RF11)
between the committee and Pfizerthroughout study conduct.
3.4.Reporting Team
The reporting team is designat ed by Pfizerand is comprised of a reporting s tatistician and
reporting p rogrammer(s) . For the P hase 2/3 portion of C4591001 study a medical monitor
and clinical scientist is also part of the reporting team. The reporting team are not members
of the study team for any of the studies being reviewed b y the committee and who will
maintain independence from the study team for the duration of the trial . The primary
responsibilities of the reporting team are:
Compileand provide unblinded outputto the committee for review .
Writethe closed committee report, including a textual summary of unblinded findings.
Coordinat eappropriate operational support activities from a dedicated team, including a
reporting p rogrammer (s).
Maintain copies of the review meeting materials for each meeting in a secure area with
restricted access .
Serve as the primary contact for all data -related issues . If the committee requires
additional data, the request and supporting rationale will be made via email to the
reporting statistician (who may elect to consult with the designated Pfizer management ).
Once the request is agreed, the reporting statistician will provide the data /outputto the
committee .
During the Phase2/3portionof the C4591001 study the unblinded medical monitor will
conduct ongoing review of COVID -19 illness cases .
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3.5.StudyTeam
The study teamincludes clinician, clinical lead, study statistician , and safety risk lead, and
other team members as appropriate . The primary responsibilities of the study teamare:
Ensurequalified study team personnel are available to review blinded (ifapplicable)
safety data per the safet y surveillance review plan for the duration of the trial in order to
complement the committee ’s safety role and fulfill Pfizer’s obligation to monitor patient
safety.
Selectthe committee chairperson and members.
Ensure app ropriate study conduct and preservation of the study blind (if applicable) to
ensureoverall study integrity is maintained.
Document in a written agreement (e.g., contract) the terms of each committee member’s
participation and indemnify ingall committee members.
Appoint the committee liaison.
Appoint the reporting team (including statistician ,reporting p rogrammer[s] and medical
monitor)not associated with the study team.
Prepareopen session meeting minutes.
Ensure that all written records are filed appropriately in the Trial Master File (TMF).
Prepare and implement the committee charter .
Provideto the committee the studyprotocol (and any subsequent protocol amendments) .
Notifythe committee of any significant new safety information (e.g .,toxicology
information, potential safety signal, and data from other clinical trials) .
Implement the committee recommendations once en dorsed by Pfizermanagement .
Promptly reviewand respond to all committee recommendations andprovide the
committee with a summary of actions taken in response to its recommendations (as
described in Section 6.2Communication of Recommendations ).
Maintain committee records other than closed session meeting minutes and CT22-GSOP-
RF11throughout study conduct.
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Archiveallrecords at the end of the study .
Submitthe committee charter to the Food and Drug Administration ( FDA)and other
regulatory authorities (RA)when appropriate .
Organize and facilitate committee meetings, including logistical support such as
identifying meeting dates and locations and providing assistance with travel
arrangements.
4.COMMITTEE MEETINGS
4.1.Meeting Schedule/Frequency
A start-upmeeting (refer to Section 4.2Start-up Meeting) will be scheduled with the
committee and members of the study team.
The first committee meeting to review study data will be scheduled no later than within the
first month of the first participant dosed with BNT162 vaccine candidates andsooner if
needed.
Thereafter, the committee will meet in person or via teleconference as required by the
protocolto review cumulative safet y data, efficacy data at the time of interim analy sesand to
make risk- benefit assessments until the study in the program is complete or at intervals
determined based on availability of key study data. It is anticipated that regular scheduled
meetings wi lloccur approximatelymonthly. The frequency of DMC meetings may decrease
(with agreement between Pfizer and the DMC) as the COVID vaccineprogram matures
howeverno fewer than two meetings per y ear will be scheduled .
During Phase 2/3 portion of the C4591001 study , themeeting frequency for cumulative data
review will be determined basedonavailability of key study data. DMC meetings may occur
weekly and DMC members will be expected to convene at short notice due to the accelerated
pace and critical need of the study if required. The chairperson and Pfizerhave the discretion
to change the meeting frequency (e.g. ifenrollment is slow) or request addit ional ad hoc
meetings with the rationale documented appropriately .
4.2.Start-up Meeting
As soon as possible after the com mittee is formed the committee members, the reporting
statistician, and members of the study team will meet to discuss the operational details of the
committee and the C4591001 protocol . The committee will review and provide input on
Pfizer’sproposals for data to be monitored, frequency of reviews, methods for review, and
criteria for making recommendations to Pfizer.
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The committee members , the reporting team, and members of the s tudy team will meet
initially to agree on:
Dataand frequency of data outputs to be provided to committee members outside of
planned meetings
Study conduct issues of interest during review meetings,
Data elements and statistical methods to be included in safet y and efficacy review(s),
List of tables, listings, and figuresand mock -ups,
Procedural issues such as meeting frequency and format, timing of data receipt and
format (including table layouts), definition of a “quorum”(comprising of the Chair,
Statistician and one Clinician) and handling of meeting docu mentation, and
Criteria and process for unblinding the data and maintaining confidentiality of
unblinded results (in the case of a blinded trial or an open -label trial in which the
dissemination of such information is restricted).
For E-DMCs established for safety monitoring, the charter must be approved before first
subject first visit ( FSFV). (It is permissible to meet this requirement with approval of a
preliminary version of the charter ; in this situation, t he subsequent version of the charter
must be approved before the first scheduled time the committee views unblinded data from
the trial.)
For all other E-DMCs the charter will be finalized and approved prior to the first review
meeting.
4.3.Review Meetings
The committee will convene to review study conduct and safety data at determined intervals
after the start -up and initial safet y review meetings . The frequency of meetings will be
dependent upon availability and nature of data to be reviewed and will be agreed between
Pfizer and the Chair. Additionally, the committee will convene to review data on an as -
needed basis (e.g ., a stopping rule is met, to review reports of COVID-19-like illnesses,
unexpected potential safety signal or study conduct concerns) . Data listings and summaries
will be supplied to c ommittee members b y the reporting statistician via secure electronic
meansat least 24 hoursprior to the meeting but may be up to 5 day s priorif possible .The
study team will present relevant information on new studies prior to the delivery of the first
dataset for these studies.
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4.4.Review Meeting Format
Eachreviewmeetingwill consist of an open and a closed session (when needed). The
committee and study teamwill be unblinded during Phase1 of the C459100 1study (to
identify preferred vaccine candidate(s), dose level(s), number of doses and schedule of
administration) but not during Phase 2/3 (expanded cohort and efficacy part).No separate
open and closed sessions will be requ ired until the study reaches Phase 2/ 3 (expanded cohort
andefficacy part)including other studies in the program .
These sessions will correspond with the type of briefing materials the committee will receive .
4.4.1.Open Session
The open session provides an opportunity for the committee to interact with members of the
study team as applicable, for example to review study status, to discuss dose -escalation
decisions made b y the IRC, and to discuss AEsthatmet the stopping rule criteria as
applicable. In addition, issues relating to the conduct of the study /studies, potential impact of
external data on the study /studies, or other topics defined in the open session of the briefing
materials can be discussed.
4.4.2.Closed Session
The closed session is the portion of the meeting where the committee discusses an y
unblinded results, deliberates over an y issues,and votes on recommendations to Pfizer. Only
committee members attend the closed -session meeting; however, the reporting statistician
and/or the committee liaison may attend all or part of the closed -session meetings with
concurrence of the committee chairperson .
Debriefing session
Following the closed session, the committee will meet again with Pfizerrepresentatives to
relay comments made by the c ommittee .
4.5.Voting Procedure
All committeemembers are voting members and are expected to participate in all meetings
and voting forums. Every effort should be made in scheduling meetings to ensure that all
members can participate . Ifall members are unable to participate in a meeting, the chairperson
and at least one additional clinician must participate in voting. Discussions and decisions
requiring expert statistical interpretation of study data require that every effort be made to include
the committee statistician. Discussions and deci sions regarding pause or termination of study
vaccination require that every effort be made to include all committee members. In the event of a
split vote, the chairperson will make the final decision concerning the committee ’s
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recommendation . If the chai r cannot participate, he /shewill delegate his /herrole to another
member of the committee .
At each meeting, the committee members will vote and provide one of the recommendations
listed inSection 6.1Recommendations.
The recommendations regarding the primary endpoint should be in accordance with the
guidance provided in this charter, the protocol , or the SAP(or other document, as
appropriate, e.g., interim anal ysis plan).
4.6.AD HOC Meetings for Emergent Safety Data
In the event that the committee is convened for an ad hocmeeting to evaluate emergent data,
processes other than those outlined in this charter may be undertaken on the recommendation
of and/or with the express consent of the committee c hairperson in order to ensure patient
safety within the trial . Any alternative processes will be documented and justified in the
committee meeting minutes. In some instances, when not all committee members are able to
attend at short notice, it is expected that a minimum of 3 members will meet. At each
meeting, the committee members will vote and provide one of the recommendations listed in
Section 6.1 Recommendations.
4.7.Meeting Minutes
The committee chair is accountable for closed session meeting minutes and may delegate the
act of recording minutes during the meeting. Committee members will review and agree to
the minutes before th ey are finalized. At a minimum the minutes should record the following
information:
Who attended the meeting;
Action items created during the meeting including who is responsible for the action;
Any resolution of action items from a previous meeting;
Any issues or concerns identif ied during the review of the data with brief rationale for the
concern;and
5.DATA PROVIDED TO THE COMMITTEE AND PARAMETERS TO BE
MONITORED/REVIEWED B Y THE COMMITTEE
5.1.C4591001 Study Only
The committeewill review all data on a regular basis (see Section 4.1and below) and during
Phase 1will also review data from the BioNTech German study as it becomes available.
Committeereviews will allow earl y detection of signs of efficacy or disease enhancement
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with corresponding earl y expansion of testing of vaccine candidates, doses, or regimens to
larger numbers of subject or, conversel y, curtailment of testing for other candidates , doses, or
regimens. Immunogenicity data may also be reviewed. Thecommittee chairperson will
communicate an y required action according to the communication plan (refer to Section 6
Communication Plan Between Pfizer and the Committee ).
5.1.1. Serious Adverse Events
All SAEs deemed unexpected and related to BNT162 SARS -CoV-2 RNAvaccines, either by
the investigator or Pfizer (also known as SUSARs [suspected unexpected s erious adverse
reactions]), willbe forwarded to the committee at the same time as they are report ed to the
RAs, investigators, and institutional review boards (I RBs)/ethics committees (ECs). The
term “unexpected” refers to an event that is either not listed in the I nvestigator ’sBrochure
(IB)Reference Safety Information section or is of greater severity or specificity than that
listed in the IBReference Safety Information section.
All SAEs collected through 6 months after the vaccination schedule is completed will be
reviewed contemporaneously . Additionally , SAE data from the ongoing BioNTech clinical
trial (BNT162 -01)will be provided to the committeefor information during the Phase 1
portion of the C45 91001 study as it becomes available to ensure a comprehensive overview
of information of the BNT 162vaccines is available .
5.1.2. Other Safety
Cumulative data of reactogenicity events and unsolicited adverse events (including that from
the ongoing BioNTech clinical trial as it becomes available in Phase 1) will be reviewed on a
regular basis during scheduled committeemeetings. Contemporaneous review of related AEs
up to 1 month after completion of the vaccination schedule will be performed . In addition,
during Phase 2/3 the committee will review all AEson a weekl y basisuntilsafety data
through 7 days after dose 2 from the first 360 participants has been submitted to regulatory
authorities. The committee will schedule an adhoc meeting if deemed necessary .
The committee will meet as soon as possible to review all available relevantdata when an y
stopping rule is met . Please refer to sections 8.2.3 and 10.7of theC4591001 protocol for
stopping rules.
5.1.3.Surveillance of Events That Could Represent Enhanced COVID-19 Disease
Because within the course of COVID -19, the illness caused by SARS-CoV-2 infection, the
onset of an exaggerated adaptive immune response and containment of viral replication in
some instances is associated with a “cy tokine storm” that accompanies clinical deterioration,
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patient profiles of all nucleic acid amplification test(NAAT)-confirmed cases will be
reviewed contemporaneously by the commi tteeduring Phase 1 of the study .
In Phase 2/3 , there will be planned reviews of the vaccine/placebo split of protocol-defined
severeCOVID-19cases atthetime of efficacy /futility analyses. The DMC will review this
data and make recommendations base don the guidance outlined in Section 10.7 of the
protocol: S topping and alert rules for severe dise ase defined.
Additionally , in Phase 2/3, the unblinded team supporting the DMC, including an unblinded
medical monitor, will review cases of severe COVID -19 as they are received and will review
AEs at leas t weekly for additional potential cases of severe COVID -19. At any point, the
unblinded team may discuss with the DMC chair whether the DMC should review cases for
an adverse imbalance of cases of COVID -19 and/or severe COVID -19 between the vaccine
and placebo groups. If so, the DMC will then meet to review available severe COVID-19
cases to determine whether the observed imbalance should result in modifications to the
study.Please refer to section 8.2.4 of the protocol for details.
In addition to the above , data regarding COVID- 19 confirmed illnesses reported in the
BioNTech study will be reviewed by the committee when information is available.
The purpose of these reviews will be to identify whether any features of each case appear
unusual, greater inseverity, compared to available information at the time of review.
Indicators of severit y may include accelerated deterioration, need for hospitalization, need
for ventilation, death. Observed rates of these indicators will be compared with what could be
expected in a similar population to the study participants based upon available information at
the time of review (for Phase 1 and 2/3) and to compare cases in active vaccine and placebo
recipients in Phase 2/3 (whenPfizerstaff will be blinded) .
5.1.4.Immunogenicity
The DMC may review safety and immunogenicity data prior to expansion into Phase 2/3.
5.1.5.Efficacy
The DMC will assess efficacy data for efficacy and/or futility during the Phase2/3 portion of
theC4591001 study as defined in the protocol .
5.2.All Other Studies
5.2.1.Serious Adverse Events
All SAEs deemed unexpected and related to BNT162 SARS -CoV-2 RNA vaccines , either by
the investigator or Pfizer (also known as SUSARs [suspected unexpected serious adverse
reactions]), will be forwarded to the commit tee at the same time as they are reported to the
RAs, investigators, and institutional review boards (I RBs)/ethics committees (ECs). The
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term “unexpected” refers to an event that is either not listed in the I nvestigator’s Brochure
(IB) Reference Safety Information section or is of greater severity or specificity than that
listed in the IB Reference Safety Information section.
All SAEs collected through 6 months after the last dosewill be reviewed. Studies in which
SAEs are followed for longer timepoints m ayalso be reviewed b y the committee.
5.2.2. Other Safety
Cumulative data of reactogenicity events, unsolicited adverse events, and clinical laboratory
assessments (if applicable) from other studies in the program will be reviewed on a regular
basis during scheduled committee meetings, as described in Section 5.1.2. Data may be
blinded or unblinded depending on stud y design.
5.2.3.Immunogenicity
The DMC may review immunogenicit ydata.
5.2.4.Efficacy
The DMC will assess efficacy and/or futil ity for all other studies if appropriate.
5.3. Provision of Study Data to the Committee
The reporting statistician is the primary channel for providing output /reports to the
committee. Approximately 24 hours to up to 5calendardays prior to each reviewmeeting
thereporting statistician will transmit all appropriate study data (as described in Section 5
Data Provided to the Committee and Parameters to be Monitored/Reviewed by the
Committee )via secure electronic means to the committee members.
Committee members must handle all study data in accordance with the confidentiality
agreement in their contract. Any queries on the data are to be made to reporting statistician
and any requests for additional data must be communicated in writing (e.g., meeting minutes)
via secure electronic mea ns to the reporting s tatistician with supporting rationale for such
requests. The reporting s tatistician may consult with the Vaccine Research &Development
Clinical and Statistical Heads (or the IRC if applicable) prior to acting upon the request . If
the study is blinded, the nature and content of the query requests may not be shared with the
study team(s).
5.3.1.Open Session Data
Prior to each review meeting, the committee will receive the following summary data
combined across or summarized by the vaccinegroups, depending on study phase,regarding
the progress of the trials.
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Study conduct issues (e .g., enrollment status, eligibility violations).
Demographic and other baseline characteristics.
Dose-escalation decisions made by the IRC as applicable .
Actions taken b y the IRC in response to events that met the stopping rule criteria as
applicable.
5.3.2.Closed Session Data
Prior to review meetings, the committee will receive the safety data indicated below
summarized/analy zedby vaccinegroup. Additionally , the committee will receive relevant
subject data l istings.Closed sessions will beconducted during the blinded stage (Phase 2/3)
of the C4591001 study .
Study status.
Demographics .
Reactogenicit y data(up to 7 day s post vaccination) .
AEs and SAEs.
AEs associated with withdrawal .
Laboratorydata when available .
Significant findings identified by the clinician/clinical lead, who will review blinded
(during C4591001 blinded Phase 2/3 portion but will be unblinded during Phase 1)
safety data as specified in the safetysurveillance reviewplan.
Significant findings identified by the IRC,who will review unbli nded safet y data as
specified in the IRC charter.
Data from interim anal yses of safety , efficacy, and immunogenicit y as defined in the
statistical analy sis plan.
5.4.Database Information
All data provided to the committee will be from a dy namic database that is continually
updated or revised as new information becomes available. A copy of the database snapshot
used for the reports will be maintained . Tables, listings, and f igureswill be annotated with
the date on which they were generated .
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6.COMMUNICATION PLAN BETWEEN THE PFIZER AND THE COMMITTEE
The expected flow of information and recommendations aredepicted in Figure1.:
Figure 1:
* For example, open session meetings, blinded SAE reports, additional analysis/data reque sts, committee meeting logistics
† Committee liaison is part of the Reporting Team; During the Phase 2/ 3portion of the C4591001 study , an unblinded medical monitor
and unblinded Clinical Scientist will be included as part of the Reporting Team . Communication between the DMC and study team
occurs through the committee liaison during Phase 2/3.
NB. C4591005 is sponsor unblinded throughout
Investigators,
Ethics Committee,
etc
Other Communication (blinded)* :
Committee
Reporting
Team†
Study Team
Members
Blinded
BioNTech
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6.1.Recommendation s
After each meeting, the committee will provide one of the following recommendations (for
each stud y reviewed) to Pfizervia CT22-GSOP-RF11:
Withhold final recommendation until further information/data is p rovided.
Continue the study or studiesas designed.
Modify the study or studiesand continue .
Stop the studyor studies.
Additionally , the committee may be asked to answer study related questions (e.g., concerning
operational challenges, impact of findings from Pfizer’s safety data review or impact of
emerging external information) provided b y the study team. The answers to the questions
will be provided with t he committee recommendation to Pfizermanagement via the
committee liaison.
The recommendations should be in accordance with the guidance provided in th is charter, th e
protocol,or the SAP(or other document, as appropriate, e.g., interim analysis plan) .
6.2.Communication of Recommendation s
For each review meeting, o nce a committee recommendation has been finalized the
committee chairperson will convey the recommendation in writing within thetimelines listed
on CT22- GSOP-RF11. The written communication will consist of the CT22-GSOP-RF11
indicating the committee ’s recommendation and sufficient information to explain the
rationale for an y recommendation will be transmitted by secure electronic meansto the
committee liaison.
The final decision to accept or reject the committee’s recommendation resides with Pfizer
management and will be communicated to the committee chairperson in writing. Review of
committee recommendation will be conducted in accordance with CT22- GSOP-RF11.
6.3.External Pfizer Communication
The committee ’s recommendation, together with Pfizer’sresponse, will be summarized by
the study team who will be responsible for communicating to all active investigators
participating in th e trialand toBioNTech representatives . The investigators and BioNTech
will be informed about the decision to continue the trial, to stop the trial, or to implement
modifications to trial procedures, on a monthly basis.
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6.4. Pfizer Internal Safety Review Co mmittee
Pfizer has established several ad hoc Internal Safety Review Committees (ISRCs), one for
each BU/RU. The ISRC for a BUis properly firewalled from all study teamsconducting
trials sponsored b y that unit . The primary objective of an ISRC is to assess specific events
that may constitute a safety concernin an unblinded manner . The assessment could result in
expedited reports to regulators as required in FDA Final Rule (2010) and EU CT -3 (2011).
The assessment may also lead to safet y-related pro tocol changes . When necessary , an ISRC
could look at the occurrence of the specific events across multiple studies in a development
program.
The activities of an ISRC are intended to be complementary and supplemental to existing
Pfizer safet y and risk m anagement processes , including this committee . There is a charter for
the ISRC describing in detail the purpose, composition ,and operations of an I SRC. The
charter is available upon request.
There may be several interactions between an I SRC and this committee , including :
When the I SRC accepts a request from the signal management lead to review specific
events, the ISRC c hair will notify the committee chairperson that a request has been
made and that a review is to be conducted with a target date (t ypically within 30 calendar
days of the request) .
The committee liaison will supply the ISRC chair a copy of the current committee
charter, open meeting minutes and c orrespondences from the committee regarding issues
for which the ISRCis currentl y being consulted.
ISRC chair will communicate review findings with the committee chairperson .
If no safety concern is identified, the ISRC will communicate this conclusion to the
signal management lead with a cop y to the committee .
If a safety concern is identified, the I SRC chair will communicate its findings to the
committee chairperson by an appropriatel y secure means . The written communication
contains the I SRC’s rationale and final assessment. (As the findings are ty pically based
on unblinded data, they must not be shared with the study team at this stage.)
The committee chairperson is requested to acknowledge receipt of the ISRC
communication as soon as possibl e. The committee considers the findings identified by
the ISRC but is not obligated to act on them.
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Where disagreement exists between the recommendations of the I SRC and the
committee , the two committees attempt to reach consensus through additional
communication .
The final decision to accept or reject the committee’s and/or ISRC’srecommendation
resides with Pfizermanagement .
The safety data (tables, listings, and reports, etc.) received by the I SRC for review are
kept confidential and will be disclo sed to the committee upon request from the
committee chairperson .
7.WRITTEN RECORDS
The committee liaisonwill maintain written records of all closed session meeting minutes,
CT22-GSOP-RF11,and materialsreviewed by the committee, and communications between
the committee and Pfizer. These documents are considered proprietary and confidential and
must be available for inspection upon request from RAs. Upon completion of the
committee’s responsibilities, the study team will obtain all written records for archiving.
7.1.Deliverables to Pfizer
The following are the deliverables from the committee chairperson to the committee liaison .
Aftereach committee review meeting:
CT22-GSOP-RF11.
Closed session meeting minutes .
7.2.GeneralProject File
The study team will compile and maintain the following document sandcorrespondence
throughout stud y conduct .
Any relevant correspondence between the committee and Pfizer .
Committee c harterand any amendments.
Current IB.
Protocol and protocol amendments.
Curriculum vitae for each committee member.
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CT22-GSOP-RF01 for each committee member.
Minutes from each open session meeting .
7.3.Unblinded data in SAS ® Datasets
The treatment assignment blind will not be broken in the project database for Phase 2/3 of
the study. The unblinded treatment assignment information will be merged
programmaticall y with the study datasets using SAS ®. Unblinded SAS® datasets and
program files will be stored and managed in an area that is separate from the general project
area and in accessible except to members of the reporting t eam.
8.CHARTER HISTORY
Version Date
(dd-Mmm-yyyy)Summary of Changes
1 29 -Apr-2020 N/A
2 10 -Jul-2020 Updated to reflect Protocol Amendment 4
3 17 -Aug-2020 Updated to reflect Protocol Amendment 5
4 22 -Oct-2020 Updated to include C4591005 Japan Study
5 0 4-Nov-2020 Updated to include 3 additional Programmers and an
unblinded Clinical Scientist to the Reporting Team
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Appendix 1.Committee Membership Log
The following outlines the key selection criteria for membership into the E -DMC:
Relevant clinical, region an d/or drug development expertise
Expertin the field of Infectious Diseases and/or Statistics
Experience serving on a DMC
Required time commitment based on the scope of responsibilities
The committee consists of the following members (past and present).
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Member Affiliation/Address Role * Dates of
MembershipBiography
Jonathan
Zenilman,
MDInfectious Diseases
Division
Johns Hopkins Bay view
Medical Center
Baltimore, MD, US
Tel: +1 410 440 9729Chair 03-April-2020Infectious
Diseases
Kathryn
Edwards,
MDVanderbilt Universit y
School of Medicine 1300
Falkirk Court, Nashville,
TN 37221
Tel: +1 615-429-3226E-DMC
member07-April-2020 Pediatric
infectious
Diseases
Robert
Belshe,
MDDivision of I nfectious
Diseases & Immunology
Saint Louis Universit y
Medical Center
714 Schiele Ave,
San Jose, CA 95126
Tel: +1 314 496 1033E-DMC
member03-April-2020Infectious
Diseases and
Immunology
Lawrence
Stanberry ,
MDColumbia University
456 Riverside Drive, Apt
8A, New York, NY, 10027
Tel: +1646-330-8329E-DMC
member07-April-2020 Pediatric
Infectious
Diseases
Steve Self,
PhDFred Hutchinson Cancer
Research Center
Vaccine and Infectious
Disease Division
1100 Fairview Avenue
North, M2- C200, Seattle,
WA 98109, USA
Tel: +1206-915-9617E-DMC
Biostatistician02-April-2020Professor
Emeritus,
Biostatistics
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*Initial date of membership is the date the effective date of the contract signed b y the
committee member .
Note:Curriculum vitae are on-file at Pfizerand maybe accessed by contacting the Study
Team.
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Appendix 2.Plan to Control Dissemination of Results
For studies that require such a plan, this will be documented in a stud y-level document that
will be filed in the TMF.
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Appendix 3.Key Contacts
VaccineResearch & Development Clinical and Statistical Heads
Name* Contact Information
William Gruber,
MDSenior Vice President, Vaccine Clinical Research &Development
401 N Middletown Road
Pearl River, NY 10965
USA
Tel:+1 845-602-3484
[email protected]
Stephen
Lockhart MDVice President Head of Europe and Asia -Pacific, Vaccine Clinical
Research and Development
Horizon Building
Honey Lane
Hurley
SL6 6RJ
United Kingdom
Tel: +44 1628 515538
Stephen.P.L [email protected]
Kenneth Koury ,
PhDHead of Statistics and Modeling, Vaccine Clinical Research &
Development
401 N Middletown Road
Pearl River, NY 10965
USA
Tel: +1 845-602-2547
Kenneth.Koury @Pfizer.com
Dina Tresnan
DVM, PhDSafety Surveillance and Risk Management
280 Shennecossett Rd, Groton, CT 06340,
USA
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Tel: +1 (860) 581-0880
[email protected]
Committee Liaison
Name* Contact Information
Xia Xu(Phase 1
of study only)Director
Pfizer, Inc
500 Arcola Road
Collegeville PA 19426
USA
Tel:+1 484-865-7762
[email protected]
Satrajit
Roychoudhury ,
PhD (Phase 2/3
of the study )Senior Director
Pfizer, Inc
USA
Tel: +1 908-901-8106
Cell: +1 862-216-5181
satrajit.roy choudhury @pfizer.com
Reporting Team Members (Unblinded)
Name* Contact Information Role
Satrajit
Roychoudhury ,
PhDSenior Director
Pfizer, Inc
USA
Tel: +1 908-901-8106
Cell: +1 862-216-5181
satrajit.roy choudhury @pfizer.comBiostatistician
WeiWei Xiong Senior Associate
Pfizer, Inc
500Arcola RoadStatistical
Programming
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Collegeville PA 19426
USA
Tel: +1 905-818-6801
[email protected]
Sridhar Guduru Statistical Programming Lead Manager
Pfizer, Inc
500 Arcola Road
Collegeville PA 19426
USA
[email protected]
Programming
Rong Zhang Senior Statistical Programming Lead
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road,
Pudong ZhangJiang Hi -tech. Park, Sha nghai,
China, 201203
[email protected]
Programming
Chen Xu* Senior Statistical Programmer
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road,
Pudong ZhangJiang Hi -tech. Park, Shanghai,
China, 201203
[email protected]
Programming
Huan Liu* Senior Statistical Programmer
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road,
Pudong ZhangJiang Hi -tech. Park, Shanghai,
China, 201203
[email protected]
Programming
Jiyang Chen* Senior Statistical Programmer
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road, Statistical
Programming
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Pudong ZhangJiang Hi -tech. Park, Shang hai,
China, 201203
[email protected]
Bochen Zhu* Senior Statistical Programmer
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road,
Pudong ZhangJiang Hi -tech. Park, Shanghai,
China, 201203
[email protected]
Programming
Ran Xiong * Senior Statistical Programmer
4/F, Building 3, Lotus Business Park, Lane
60, Naxian Road,
Pudong ZhangJiang Hi -tech. Park, Sha nghai,
China, 201203
[email protected]
Programming
Shon Remich
MDSenior Director
Pfizer, Inc
500 Arcola Road
Collegeville PA 19426
USA
Tel:+1 215-872-3633
+1 301-642-6809
[email protected] Medical
Monitor
Lisa Moyer**Senior Manager
Pfizer, Inc
500 Arcola Road
Collegeville PA 19426
USA
Tel: +1 (484) 8658348
Lisa.L.Mo [email protected] Clinical
Scientist
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* Due to the volume and frequency of the unblinded tables, figures and listings (TLFs) that
would need to be generated and undergo quality checksduring Phase 2/3 of the study ,
additional statistical programming support is required. These members will be involved with
providing support for the unblinded TLFs for safety and immunogenicit y only. They will be
restricted from efficacy at the Interim Anal yses.
** The unblinded Clinica l Scientist (CS) will assist with responding to subject level queries
using relevant data s ystems during DMC closed sessions, w hilstthe unblinded medical
monitor(MM)is required to address medical questions and interpretation. The MM and CS
are complimen tary and the paring mimics how Pfizertypically conduct safety reviews for
clinical trials for all studies.
Study Team Members
Name* Contact Information Role
Nicholas
Kitchin, MDSenior Director, Vaccine Clinical Research
and Development
Horizon Building
Honey Lane
Hurley
SL6 6RJ
United Kingdom
Tel: +44 7557 202435
[email protected] Study Lead
Judith Absalon,
MD, MPHSenior Director, Vaccine Clinical Research
and Development
401 N Middletown Rd
Pearl River, NY 10965
USA
Tel: +1 845-602-1685
[email protected] DMC responsible
Clinician
Alejandra
Gurtman, MDVice President
Pfizer Vaccine Clinical Research and
Development
401 N Middletown Rd
Pearl River, NY 10965 Study Clinician
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USA
Tel:+1 845-602- 2842 Cell 201 -290-0489
Fax:+1 845 474 3219
[email protected]
Susan Mather,
MDSenior Director, S afety Surveillance and Risk
Management
500 Arcola Road
Collegeville, PA 19426
USA
Tel: +1 (484) 8652514
[email protected] Risk Lead
Ruth Bailey Director, Clinical Scientist
Horizon Building
Honey Lane
Hurley
SL6 6RJ
United Kingdom
Tel: +44 1628 515654
ruth.bailey @pfizer.comLead Clinical
Scientist
Harpreet Seehra Senior Manager, Clinical Scientist
Horizon Building
Honey Lane
Hurley
SL6 6RJ
United Kingdom
Tel: +44 7901788821
[email protected] Responsible
Clinical Scientist
Xia Xu Director
Pfizer, Inc
500 Arcola Road
Collegeville PA 19426
USAXia Xu(Study
Biostatistician
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Tel: +1 484-865-7762
[email protected]
James Baber
MBChB, MPHDirector, Clinician, Global Medical Monitor
Level 15- 18, 151 Clarence St
Sydney
NSW 2000
Australia
Tel: +61 419410413
[email protected]
C4591005 Study
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Appendix 4.List of Studies (if committee is to oversee multiple studies)
Study Date Added
(dd-Mmm-yyyy)
C4591001 29-Apr-2020
C4591005 22-Oct-2020
Please refer to the current C4591001 and C4591005 protocolsfor details of the study
designs.
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C4591001
Investigational BNT162 Vaccine Program
PF-07302048
Version : 2.0
Date: 11-June-2020
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TABLE OF CONTENTS
1. INTRODUCTION .................................................................................................................4
1.1. Study Design .............................................................................................................4
1.2. Purpose of the Committee .........................................................................................4
1.3. Committee Close- Out ................................................................................................4
2. COMMITT EE MEMBERSHIP. ............................................................................................5
2.1. Conflicts of Interest ...................................................................................................5
2.2. Confidentiality Agreement/Contract .........................................................................5
2.3. Authorship .................................................................................................................5
3. ROLES AND RESPONSIBILITIES .....................................................................................5
3.1. Committee Members .................................................................................................5
3.2. Committee Chairperson .............................................................................................6
3.3. Committee Liaison ....................................................................................................6
3.4. Study Team ...............................................................................................................7
4. COMMITTEE MEETING S...................................................................................................8
4.1. Meeting Schedule/Frequency ....................................................................................8
4.2. Start-up Meeting ........................................................................................................9
4.3. Review Meetings .....................................................................................................10
4.4. Review Meeting Format ..........................................................................................10
4.5. Voting Procedure .....................................................................................................10
4.6. AD HOC Meetings for Emergent Safety Data ........................................................11
4.7. Meeting Minutes .....................................................................................................11
5. DATA PROVIDED TO THE COMMITTEE AND PARAMETERS TO BE
MONITORED/REVIEWED B Y THE COMMITTEE .......................................................12
5.1. Provision of Study Data to the Committee ..............................................................12
5.2. Data for Review Meetings .......................................................................................12
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5.2.1. Open Session Data .....................................................................................12
5.2.2. Safety Review for Stopping Rules for Sentinel Cohort ..............................13
5.3. Database Information ..............................................................................................14
6. COMMUNICATION PLAN BETWEEN PFIZER AND THE COMMITTEE ..................14
6.1. Overview of the Communication Plan ....................................................................14
6.2. Recommendations ...................................................................................................15
6.3. Communication of Recommendations ....................................................................16
6.4. External Pfizer Communication ..............................................................................16
6.5. Pfizer Internal Safety Review Committee ...............................................................17
7. WRITTEN RECORDS ........................................................................................................18
7.1. Deliverables .............................................................................................................18
7.2. General Project File .................................................................................................19
7.3. Unblinded data in SAS® Datasets ..........................................................................19
8. CHARTER HISTORY.........................................................................................................19
APPENDICES
Appendix 1. Committee Membership Log ..............................................................................20
Appendix 2. Plan to Control Dissemination of Results ...........................................................23
Appendix 3. Key Contacts .......................................................................................................24
Appendix 4. List of Studies (if committee is to oversee multiple studies) ..............................26
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1. INTRODUCTION
This i nternal r eview committee (IRC) (hereafter referred to as “the committee”) is a single,
expert advisory group including one or more Pfizer colleagues (who are not directly involved
in the conduct of this study) established to oversee this Pfizer -managed trial (C4591001).
The primary rationale for establishing the committee is to make certain that appropriate
safeguards are in place to help ensure the safety of participant s. The IRC will be responsible
for reviewing safety and immunogenicity data at multiple planned timepoints in the C4591001 study, as well as in the event a stopping rule is met .
Pfizer is responsible for conducting this study. BioNTech is the regulatory sponsor of this study.
1.1. Study Design
C4591001: A Phase 1/2, Placebo -Controlled, Randomized, Observer-Blind, Dose-Finding
Study To Describe The Safety, Tolerability, Immunogenicity, And Potential Efficacy Of
SARS COV-2-RNA Vaccine Candidates Against COVID 19 In Healthy Adults Please refer to the curren t C4591001 protocol for details of the study design
1.2. Purpose of the Committee
The committee will review accumulating safety and immunogenicity data from the above-
mentioned study during Stage 1 and 2. The committee will advise the study team(s) and senior management regarding the safety of current participants, as well as the continuing scientific validity and progress of the trial. The committee will review safety data which may contribute to stopping rules at ad hoc meetings and all available safety data at regular meetings (Refer to Section 5 for details).
In addition to safety review by the committee, qualified Pfizer personnel will review safet y
data as specified in the Safety Surveillance Review Plan and will inform the committee of significant findings.
1.3. Committee Close- Out
The committee will have completed its work and be dissolved when final data from this
study under the scope of the IRC Charter has been reviewed.
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2. COMMITTEE MEMBERSHIP .
The committee consists of a chairperson and at least 2 additional members, as indicated in
the list of members in Appendix 1 Committee Membership Log including at least one with
medical qualifications and at least one other who is a statistician . IRC members are
colleagues who are not directly involved in the conduct of these studies.
During the conduct of the study, membership of the committee may change based on expertise needed , availability , and new conflicts of interest that war rant a change. A dated
log must be maintained in Appendix 1 reflecting any changes in membership. If any member
leaves the committee, the Pfizer will promptly appoint a replacement in consultation with the
committee chairperson , if needed .
2.1. Conflicts of Interest
Not applicable. All committee members are Pfizer employees.
2.2. Confidential ity Agreement/Contract
Not applicable. All committee members are Pfizer employees.
2.3. Authorship
Not applicable. All committee members are Pfizer employees.
3. ROLES AND RESPONSIBI LITIES
3.1. Committee Members
The primary responsibilities of the committee members are:
• Review, endorse, and implement the charter.
• Review safety data from in scope studies on a regular basis ( refer to s ection 4.1
Meeting/Schedule Frequency) throughout the duration of the trial.
• Provide an informed risk -benefit assessment and advis e the study team regarding the
continuation of the trial based on the reviewed data.
• Provide guidance, where appropriate, on additional questions presented by the study t eam
prior to review meetings .
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3.2. Committee Chairperson
The primary responsibilities of the committee chairperson are:
• Review and approve the charter on behalf of the committee members .
• Facilitate discussion by integrating differing points of view and moving the committee
towards recommendations to be provided to Pfizer in a timely fashion.
• Prepare closed session meeting minutes (or prepare via a designee) .
• Complete CT22 -GSOP -RF11 Brief Recommendation Form and submit to the senior
management team according to the communication plan (refer to s ection 6
Communication Plan Between Pfizer and the Commit tee)
• Communicate with the senior management team according to the communication plan on
behalf of the committee (refer to section 6 Communication Plan Between Pfizer and the
Committee ).
• Provide all unblinded written records to the study team for archiving.
3.3. Committee Liaison
The committee liaison is not a member of the study team for any study being reviewed by the
committee. The committee liaison is designated by Pfizer and will maintain independence
from the study team for the duration of the tr ial. The primary responsibilities of the
committee liaison are:
• Serve as the primary liaison between the committee and Pfizer management.
• Receive and distribute, according to the communication plan, the committee recommendations from the committee chairperson.
• Ensure the committee has access to timely information about the study
• Handle and maintain a record of communications between the committee and Pfizer
management .
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Manage written records (e.g., closed session meeting minutes and CT22-G SOP-RF11)
between the committee and Pfizer throughout study conduct.
3.4. Study Team
The study team includes program clinical lead, lead study clinician, clinical scientist, study
statistician and other team members as appropriate. The primary responsibiliti es of the study
team are:
• Ensure qualified study team personnel are available to review safety data (unblinded or
blinded according to the study stage) per the safety surveillance review plan for the
duration of the trial in order to complement the committee’s safety role and fulfill Pfizer ’s obligation to monitor patient safety .
• Select the committee chairperson and members .
• Ensure appropriate study conduct and preservation of the study blind ( if applicable) to
ensure overall study integrity is maintained .
• Appoint the reporting team (including s tatistician and reporting programmer[s]) not
associated with the study team .
• Prepare open session meeting minutes .
• Ensure that all written records are filed ap propriately in the Trial Master File (TMF) .
• Prepare and implement the committee charter .
• Provide the study protocol (and any subsequent protocol amendments) to the committee .
• Notify the committee of any significant new safety information (e.g., toxicology
information, potential safety signal, and data from other clinical trials) .
• Implement the committee recommendations once endorsed by Pfizer management .
• Promptly review and respond to all committe e recommendations and provide the
committee with a summary of actions taken in response to its recommendations (as
described in section 6.3 Communication of Recommendations ).
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• Maintain committee records throughout study conduct.
• Archive all records at the end of the study.
• Submit the committee charter to the Food and Drug Administration ( FDA ) and other
regulatory authorities (RA) when appropriate.
• Organize and facilitat e committee meetings, including logistical support such as
identifying meeting dates and locations and providing assistance with travel arrangements .
4. COMMITTEE MEETINGS
4.1. Meeting Schedule/Frequency
Prior to the start of enrollment in the C4591001 study, a start -up meeting ( refer to section 4.2
Start-up Meeting ) will be scheduled with the committee and members of the study team to
review the draft charter, discuss roles, scope of reviews and logistics. The committee will then meet to review safety data from C4591001
.
For each vaccine candidate/dose level/dose schedules t he IRC will meet to :
• Review safety data to inform and per mit dos ing decisions in the 18-to 55- year age cohort
(Stage 1)
• Decisions on dosing will be based on IRC review of at least 7 -day post-D ose 1 safety
data in this study and/or the BioNTech study conducted in Germany (BNT162-01).
• Note that, for candidates based upon the same RNA platform (eg, BNT162b1, BNT162b2), dose escalation for the second or subsequent candidates studied may be based upon the safety profile of the first candidate studie d being deemed acceptable at
the same, or a higher, dose level by the IRC.
• Review of safety data in the case of a stopping rule being met
• Review of safety and /or immunogenicity data to:
• Allow groups of participants of 65 to 85 years of age to proceed
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• Grou ps of participants 65 to 85 years of age will not be started until safety data for
the RNA platform have been deemed acceptable at the same, or a higher, dose level in the 18- to 55- year age cohort by the IRC.
• Select vaccine candidate(s)/dose level(s), and schedule(s) to proceed into Stage 2 ( as
appropriate).
• Select vaccine candidate(s)/dose level(s), and schedule(s) to proceed into Stage 3 .
• Review of any available safety and/or immunogenicity data generated during the
course of this study, or the BioNTech study conducted in Germany, to determine:
• Whether groups may be started at the next highest dose
• Whether any groups may not be started
• Whether any groups may be terminated early
• Whether any groups may be added with dose lev els below the lowest stated dose or
intermediate between the lowest and highest stated doses
• Contemporaneous review of all NAAT- confirmed COVID -19 illnesses
4.2. Start -up Meeting
As soon as possible after the committee is formed , the committee members , the reporting
statistician, and members of the study t eam will meet to discuss the operational details of the
committee and the protocol.
The committee members and members of the study t eam will meet initially to agree on:
• Study conduct issues of interest during review meetings,
• Data elements and statistical methods to be included in safety and efficacy review(s),
• List and/or mock-ups of t ables, l istings , figures and/or data summaries ,
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• Procedural issues such as meeting frequency and format, timing of da ta receipt and
format (including table layouts), definition of a “quorum” and handling of meeting documentation, and
• Criteria and process for unblinding the data and maintaining confidentiality of unblinded results (in the case of a blinded trial or an open- label trial in which the
dissemination of such information is restricted).
The charter will be finalized and approved prior to the first subject first dose .
4.3. Review Meetings
The committee will convene to review study conduct and safety data at determined intervals
after the start -up and initial safety review meetings . Additionally, the committee will
convene to review data on an as -needed basis (e.g ., a stopping rule is met, to review reports
of COVID -19-like illnesses , unexpected safety or study conduct concerns, when a stopping
rule is met). Committee members will be required to be available at very short notice to allow dose escalation or changes to continuation of specific groups. Data listings and summaries may be supplied to c ommittee member s prior to the meeting .
4.4. Review Meeting Format
Each review meeting will consist of an open session during Stages 1 and 2 of the study. The
committee and study team will be unblinded during Stage 1 of the study (to identify preferred vaccine candidate(s), dose level(s), number of doses and schedule of administration) and Stage 2 (expanded cohort stage). The IRC will not be required to meet during Stage 3 of the study.
No separate open and closed sessions will be required. 4.5. Voting Procedure
All committee members are voting members and are expected to participate in all meetings
and voting forums. Every effort should be made in scheduling meetings to ensure that all members can participate. I n the unlikely event that not all members are able to participate in
a meeting, a quorum requires the participation of a majority of members, one of whom must
be the Chair , one of whom must be medically qualified and the committee statistician . A
majority vote is required to make any of the above recommendations. In the event of a split vote, the chairperson will make the final decision concerning the committee’s
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recommendation . If the chair cannot participate, he/she will delegate his /her role t o another
member of the committee.
At each meeting, the committee members will vote and provide one of the recommendations
listed in section 6.2 Recommendations .
4.6. AD HOC Meetings for Emergent S afety D ata
In the event that the committee is convened for an ad hoc meeting to evaluate emergent data,
processes other than those outlined in this charter may be undertaken on the recommendation of and/or with the express consent of the committee c hairperson in order to ensure patient
safety within the trial. Any alternative processes will be documented and justified in the committee meeting minutes.
4.7. Meeting Minutes
The committee chair is accountable for open session meeting minutes and may delegate the act of recording minutes during the meeting. Committee members will review and agree to the minutes before they are finalized. At a minimum the minutes should record the following information:
• Who attended the meeting;
• Action items created during the meeting including who is responsible for the action;
• Any resolution of action items from a previous meeting;
• Any issues or concerns identified during the review of the da ta with brief rationale for the
concern;
• CT22 -GSOP -RF11 Brief Recommendation Form .
The study team will work with the committee to prepare open -session meeting minutes
that describe the meeting proceedings. The study team is responsible for filing the open-
session minutes in the trial master file (TMF).
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5. DATA PROVIDED TO THE COMMITTEE AND PARAMETERS TO BE
MONITORED/REVIEWED B Y THE COMMITTEE
The committee will review all data from the US study on a regular basis (see section 4.1 and below) and data from the BioNTech German study as they become available.
5.1. Provision of Study Data to the Committee
The study team is the primary channel for providing output/reports to the committee .
5.2. Data for Review Meetings
5.2.1. Open Session Data
Prior to each review meeting, the committee will receive summary data combined across the
vaccine groups regarding the progress of the trial . The committee and study team will be
unblinded during Stage 1 of the study (to identify preferred vaccine candidate(s), dose level(s), number of doses and schedule of administration) and Stage 2 (expanded cohort stage). No closed sessions will be required.
The committee and study team will review all available listings and summary tables of
participant s enrolled into BNT162 vaccine candidates/dose level/age group/number of doses
to allow for review of the following.
• Demographic and other baseline characteristics .
• BNT162 investigational vaccine candidate randomization assignments and study
discontinuations
• 7-day reactogenicity data.
• Discontinuation due to a dverse e vents (AEs)
• AEs and SAEs
• Laboratory data when available.
• Patient profiles of COVID -19 unplanned illness visits
• Immunogenicity data post-dose 1 when available
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• Immunogencity data post-dose 2 when available
• Deaths
If the safety profile is acceptable in the younger age group, a decision will be made to move into next dose level in that age group for each vaccine candidate in Stage 1. Review of s afety
and/or immuno genicity after dose 1 or 2 data will be required to move into the older age
group and dose escalate for each vaccine candidate in Stage 1 . The s tudy team will be
informed and recommendations will be documented using the Brief Recommendation Form
(CT22 -GSOP -RF11 Brief Recommendation Form).
Cumulative safety and immunogenicity (when available) data will be reviewed from all
participants enrolled into the study at each dose level. A recommendation will be made on
further dose- escalation. The s tudy team will be informed.
If recommendations are other than to continue the study as planned, the Joint Safety Review Team (JSRT) will make the final deci sion on study progress (CT22- GSOP -RF11 Brief
Recommendation Form). Please see the JSRT charter for further information.
5.2.2. Safety Review for Stopping Rules for Sentinel Cohort
The study team physician/designee will have access to randomization lists to unblind
participants (during Stage 1 and 2) with suspected related events in order to select BNT162
RNA platform related events for review by the committee, which may have met the study
stopping rules.
• At the open session the committee will review all available data associated with each participant who has met a stopping rule including demographics, medical history,
reactogenicity, and AE data.
The committee will recommend further actions req uired. Study team will be informed. Note
that if a stopping rule is met the DMC must meet to review all available and relevant data and also make a recommendation about continuation of the study.
• If recommendations are other than to continue the study as planned, the Joint Safety
Review Team (JSRT) will make the final decision on study progress (CT22- GSOP -RF11
Brief Recommendation Form). Please see the JSRT charter for further information.
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5.3. Database Information
All data provided to the committee will be from a dynamic database that is continually
updated or revised as new information becomes available. Tables, listings, and figures will be annotated with the date on which they were generated .
6. COMMUNICATION PLA N BETWEEN PFIZER AND THE COMMITTEE
6.1. Overview of the Communication Plan
The expected flow of unblinded information and recommendations is depicted in Figure 1:
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Figure 1
Unblinded Results and Recommendations
6.2. Recommendation s
After each meeting, the committee will provide one of the following recommendations to
Pfizer via CT22 -GSOP -RF11:
• Dose escalation in the younger age group
• Initiate dosing in the older age group
• Dose escalation in the older age group
• Expansion in non- sentin el cohort and expanded cohort
• Continue specific dose levels/vaccine candidate
• Discontinue specific dose level/vaccine candidate Unblinded Int ernal External
Committee
Senior management
endorses/discusses
recommendation if other
than continue as planned Study Team Blinded:
Investigators
IRC, IEC etc
EDMC will
be informed
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• Select final vaccine candidate and dose level
• Withhold final recommendation until further information/data is p rovided.
• Continue the study as designed.
• Modify the study and continue.
• Stop the study.
Additionally, the committee may be asked to answer study related questions (e.g., concerning operational challenges, impact of findings from Pfizer’s safety data review or impact of emerging external information) provided by the study team. The answers to the questions
will be provided with t he committee recommendation to Pfizer management via the
committee liaison (role is done by the study team for this study).
The recommendations should be in accordance with the guidance provided in this charter, the protocol, or the SAP (or other document, as appropriate, e.g., interim analysis plan).
6.3. Communication of Recommendations
For each review meeting, once a committee recommendation has been finalized the committee chairperson will convey the recommendation in writing within the timelines listed on CT22- GSOP -RF11 . The written communication will consist of the CT22 -GSOP -RF11
indicating the committee’s recommendation and sufficient information to explain the rationale for any recommendation will be transmitted by secure electronic means to the study
team . A copy of the committee recommendations will be forwarded to the JSRT by a
member of the study team.
Review of committee recommendation will be conducted in accordance with CT22- GSOP -
RF11. 6.4. External Pfizer Communication
The committee ’s recommendation, together with the senior management’s decision , will be
summarized by the study team who will be responsible for communicating to al l active
investigators participating in the trial within 2 business days if the recommendation is other
than to continue the trial as planned . The investigators and EDMC will be informed about
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the decision to stop the trial, or to implement modifications to trial procedures, as appropriate.
As required, the investigators will be instructed to submit this communication to their
respective IRB/EC. The committee’s recommendations and senior management endorsement will also be communicated to re gulatory authorities (in accordance with lo cal regulations).
6.5. Pfizer Internal Safety Review Committee
Pfizer has established several ad hoc Internal Safety Review Committees (ISRCs), one for each BU/RU . The ISRC for a BU is properly firewalled from all stu dy teams conducting
trials sponsored by that unit. The primary objective of an ISRC is to assess specific events that may constitute a safety concern in an unblinded manner. The assessment could result in
expedited reports to regulators as required in FDA Final Rule (2010) and EU CT-3 (2011). The assessment may also lead to safety -related protocol changes . When necessary, an ISRC
could look at the occurrence of the specific events across multiple studies in a development program.
The activities of an ISRC are intended to be complementary and supplemental to existing
Pfizer safety and risk management processes, including this committee . There is a charter for
the ISRC describing in detail the purpose, composition, and operations of an ISRC. The
charte r is available upon request.
There may be several interactions between an ISRC and this committee , including:
• When the ISRC accepts a request from the signal management lead to review specific
event s, the ISRC c hair will notify the committee chairperson that a request has been
made and that a review is to be conducted with a target date (typically within 30 calendar days of the request).
• The committee liaison will supply the ISRC chair a copy of the current com mittee
charter, open meeting minutes and correspondences from the committee regarding issues
for which the ISRC is currently being consulted.
• ISRC c hair will communicate review findings with the committee chairperson .
• If no safety concern is identified, the ISRC will communicate this conclusion to the signal management lead with a copy to the committee .
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• If a safety concern is identified, the ISRC c hair will communicate its findings to the
committee chairperson by an appropriately secure means . The writte n communication
contains the ISRC’s rationale and final assessment .
• The committee chairperson is requested to acknowledge receipt of the ISRC
communication as soon as possible. The committee considers the findings identified by
the ISRC but is not oblig ated to act on them .
• Where disagreement exists between the recommendations of the ISRC and the committee , the two committees attempt to reach consensus through additional
communication .
• The final decision to accept or reject the committee’s and/or ISRC ’s recommendation
resides with sponsor management .
• The safety data (tables, listings, and reports, etc.) received by the ISRC for review are kept confidential and will be disclosed to the co mmittee upon request from the
committee chairperson .
7. WRITTEN RECORDS
The study team will maintain written records of all open session meeting minutes , CT22 -
GSOP -RF11, and material s reviewed by the committee, and communications between the
committee and the Pfizer . These documents are considered proprietary and confidential and
must be available for inspection upon request from RAs . Upon completion of the
committee’s responsibilities, the study team will obtain all written records for archiving.
Closed session minutes are not appropriate to file in the TMF until the last study is complete.
7.1. Deliverables
The following are the deliverables from the committee chairperson to the study team.
After each committee review m eeting:
• CT22 -GSOP -RF11.
• IRC session meeting minutes .
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7.2. General Project File
The study team will compile and maintain the following documents and correspondence
throughout study conduct.
• Any relevant correspondence between the committee and Pfizer .
• Committee c harter and any amendments.
• Current IB.
• Protocol and protocol amendments.
• Curriculum vitae for each committee member .
• CT22 -GSOP -RF01 for each committee m ember .
• Minutes from each open session meeting .
7.3. Unblinded data in SAS ® Datasets
The unblinded treatment assignment information will be merged programmatically with the
study datasets using SAS ®.
8. CHARTER HISTORY
Version Date
(dd-Mmm -yyyy) Summary of Changes
1 29-Apr-2020 N/A
2 11-Jun-2020 • Amended that IRC decision to progress group(s) into
Stages 2 and 3 can be based upon safety and immunogenicity data after dose 1 or 2
• Clarified safety data requirements to permit dose
escalation
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• Amended that progression to participants 65 to 85 years
of age can be based upon data from the same RNA platform
• Amended that stopping rules apply to an RNA platform rather than a specific vaccine candidate
• Modified the criteria required for the IRC to determine
dose escalation in the 18- to 55- year age cohort and
advancement to groups of participants 65 to 85 years of
age
• To permit individual and group dosing alterations for the second dose of study intervention
Appendix 1. Committee Membership Log
The committee consists of the following members (past and present).
Member Affiliation/Address Role Dates of
Membership*
Kathrin Jansen ,
PhD Senior Vice President, Head of
Vaccine Research and Development
Tel: +1 845 602 5450
[email protected] Committee
member 29-April -2020
Philip Dormitzer
MD PhD VP & CSO, Viral Vaccines
401 N Middletown Rd Pearl River, NY 10965
Tel: +1 (845) 6027742 Committee
member 29-April -2020
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[email protected]
William Gruber
MD Senior Vice President, Vaccin e
Clinical Research and Development, Pfizer Inc.
401 N Middletown Rd Pearl River, NY 10965 Tel: +1 845 602 3484
[email protected] Chairperson 29-April -2020
Rob Maroko
MD Senior Director , Safety
Surveillance and R isk
Management
500 Arcola Road Collegeville PA 19426 USA Tel: +1 (484) 8658566
[email protected] Committee
member 29-April -2020
Stephen Lockhart
MD Vice President Head of Europe
and Asia- Pacific, Vaccine
Clinical Research and Development
Horizon Building Honey Lane Hurley SL6 6RJ United Kingdom Tel: +44 1628 515538 [email protected]
Committee
member 29-April -2020
Kenneth Koury ,
PhD Executive Director
Biostatistics, Vaccine Clinical Research and Development, Pfizer Inc.
Statistician 29-April -2020
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401 N Middletown Rd
Pearl River, NY 10965 Tel: +1 (845) 602 2547
[email protected]
* Initial date of membership is the date the effective date of the contract signed by the
committee member .
Note: Curriculum vitae are on -file at Pfizer and may be accessed by contacting the Study
Team .
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Appendix 2. Plan to Control Dissemination of Results
This is an observer-blinded study as the physical appearance of the BNT162 vaccine
candidates and placebo differ.
At the study site : The participant, investigator, study coordinator, and other site staff will be
blinded. The dispenser(s)/administrator(s) and those study site team members who are
involved in ensuring that protocol requirements for investigational product handling, allocation, and administration are fulfilled at the site (e .g. study manager, clinical research
associates) will be unblinded for the duration of the study. Breaking the blind by the Investigator: Blinding codes should be broken by the investigator only when knowledge of the actual treatment code is absolutely essential for further management of the participant . The method will be an electronic process via Impala.
Pfizer : For Stage 1 (dose- finding ) and Stage 2 ( expanded cohort ): Pfizer study team
members are un blinded to the vaccine assigned/received by all participants .
Pfizer : Laboratory personnel performing the immunologic assays will remain blinded to
vaccine assigned/received throughout the study. Unblinded Pfizer personnel: Randomization codes will be released to reporting team (unblinded reporting statistician and unblinded programmer) who need access to the codes to generate the summaries and participan t data listings for the review by the unblinded
committee members during Stages 1 and 2 the study. Randomization codes will be available
to the committee via the reporting team .
Release of the randomization codes to designated personnel will only be performed upon
completion of the Randomization Code Release Request Form in GRAABS. Randomization codes and unblinded data will be maintained in a secure location.
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Appendix 3. Key Contacts
Study Team Members
Name* Contact Information Role
Nicholas Kitchin Senior Director, Vaccine Clinical Research
and Development
Horizon Building Honey Lane Hurley SL6 6RJ United Kingdom Tel : +44 7557 202435
[email protected] Study Clinician
Ruth Bailey Director, Clinical Scientist, Vaccine Clinical
Research and Development
Horizon Building Honey Lane Hurley SL6 6RJ United Kingdom Tel: +44 1628 515654
[email protected] Lead Clinical
Scientist
Judith Absalon,
MD, MPH Senior Director, Vaccine Clinical Research
and Development
401 N Middletown Rd Pearl River, NY 10965
Tel: +1 845 602 1685
[email protected] Independent
Clinician
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Alejandra
Gurtman Vice President
Pfizer Vaccine Clinical Research and Development Tel +1 845-602-2842 Cell 201-290-0489
Fax +1 845 474 3219
[email protected] Independent
Clinician
Ping Li Senior Director
500 Arcola Road Collegeville PA 19426 USA Tel: +1 484 8652138
[email protected] Program
Biostatistician
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Appendix 4. List of Studies ( if committee is to oversee multiple studies )
Study Date Added
(dd-Mmm -yyyy)
C4591001: A Phase 1/2, Placebo -Controlled, Randomized, Observer -
Blind, Dose-Finding Study To Describe The Safety, Tolerability,
Immunogenicity, And Potential Efficacy Of SARS COV-2- RNA
Vaccine Candidates Against COVID 19 In Healthy Adults 29-Apr-2020
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