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Protocol C4591020 (PF-07302048 ) Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 1Protocol C4591020
A PHASE 3, RANDOMIZE D, OBSERVER -BLIND ST UDY TO EVALUATE THE
SAFETY, TOLERABILITY , AND IMMUNOGENICITY OF A LYOPHILIZED
MULTIPLE FORMULATION SOF THE VACCINE CANDIDAT E BNT162b 2
AGAINST COVID -19 IN HEALTHY ADULTS 18 THROUGH 55 YEARS OF AGE
Statistical Analysis Plan
(SAP)
Version: 21
Date: 1605April May 2021
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Page 2TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ..................... 4
APPENDI CES ................................ ................................ ................................ ........................... 5
1. VERSI ON HISTORY ................................ ................................ ................................ ............ 6
2. INTRODUCTION ................................ ................................ ................................ ................. 6
2.1. Study Objecti ves, Endpoints, and Estimands ................................ ............................ 6
2.2. Study Design ................................ ................................ ................................ ............. 8
3. ENDPOINTS AND BASELINE VARIABLES: DEF INIT IONS AND
CONVENTIONS ................................ ................................ ................................ .................. 9
3.1. Primary Endpoints ................................ ................................ ................................ .....9
3.1.1. Prima ry Immunogenicity Endpoints ................................ ............................. 9
3.1.2. Primary Safet y Endpoints ................................ ................................ ............. 9
3.1.2.1. L ocal Reactions ................................ ................................ ........... 9
3.1.2.2. Sy stemic Events (Sy stemic Event S ymptoms and Fever) ......... 12
3.1.2.3. Use of Antip yretic Medication ................................ .................. 13
3.1.2.4. Adverse Events ................................ ................................ .......... 14
3.1.2.5. Serious Adverse Events ................................ ............................. 14
3.2. Secondary Endpoints ................................ ................................ ............................... 14
3.2.1. Secondary Immunogenicity Endpoints ................................ ....................... 14
3.3. Exploratory Endpoints ................................ ................................ ............................. 14
3.4. Baseline and Other Variables ................................ ................................ .................. 15
3.4.1. Demographics, Medical History , and Phy sical Examination ..................... 15
3.4.2. E- Diary Transmission ................................ ................................ ................. 15
3.4.3. Prior/Concomitant Vaccines and Concomitant Medications...................... 15
3.5. Safet y Endpoints ................................ ................................ ................................ .....16
4. ANALYSIS SETS (POPUL ATIONS FOR ANALYSI S)................................ ................... 17
5. GENERAL METHODOLOGY AND CONVENTIONS ................................ .................... 18
5.1. Hy potheses and Decision Rules ................................ ................................ .............. 18
5.1.1. I mmunogenicit y Hypotheses ................................ ................................ ......18
5.1.2. Multiplicity Considerations ................................ ................................ ........ 19
5.2. General Methods ................................ ................................ ................................ .....19
5.2.1. Analy ses for Binary Data ................................ ................................ ............ 19
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Page 35.2.2. Analyses for Continuous Data ................................ ................................ ....19
5.2.2.1. Geometric Mean Ratios ................................ ............................. 20
5.2.2.2. Geometric Means ................................ ................................ ......20
5.2.2.3. Geometric Mean Fold Rises................................ ...................... 20
5.2.2.4. Reverse Cumulative Distribution Curves ................................ ..20
5.3. Methods to Manage Missing Data ................................ ................................ .......... 20
6. ANALYSES AND SUMM ARIES................................ ................................ ...................... 21
6.1. Primary Endpoints ................................ ................................ ................................ ...21
6.1.1. Pri mary Immunogenicity Endpoint ................................ ............................ 21
6.1.1.1. Full -Length S -Binding IgG Concentrations at 1 Month
After Dose 2 for Participants Receiving Lyophilized
Formulation in SDVs or Frozen- Liquid Formulation in MDVs .......21
6.1.2. Primary Safet y Endpoints ................................ ................................ ........... 22
6.1.2.1. L ocal Reactions ................................ ................................ ......... 22
6.1.2.2. Sy stemic Events ................................ ................................ ........ 23
6.1.2.3. Adverse Events ................................ ................................ .......... 24
6.1.2.4. Serious Adverse Events ................................ ............................. 25
6.2. Secondary Endpoints ................................ ................................ ............................... 25
6.2.1. I mmunogenicit y Endpoints ................................ ................................ ......... 25
6.2.1.1. Full -Length S -Binding IgG Levels ................................ ........... 25
6.2.1.2. Fold Rises in Full -Length S -Binding IgG Levels From
Baseline Through 1 Month Afte r Dose 2 ................................ .......... 26
6.3. Other Endpoints ................................ ................................ ................................ .......26
6.3.1. Exploratory Endpoints ................................ ................................ ................ 26
6.3.1.1. Full -Length S -Binding IgG Concentrations and/or SARS -
CoV2 Neutralizing Titers at 1 Month after Dose 2 for
Participants Receiving Frozen -Liquid BNT162b2 with L NP
Size at Upper End of Specification or Frozen- Liquid
BNT162b2 in MDVs ................................ ................................ ......... 26
6.3.1.2. Full -Length S -Binding IgG Concentrations and/or SARS-
CoV2 Neutralizing Titers at 1 Month after Dose 2 for
Participants Receiving RTU BNT162b2 or Lyophilized
BNT162b2 in SDVs ................................ ................................ .......... 27
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Page 46.3.1.3. Full -Length S -Binding IgG Concentrations and/or SARS -
CoV2 Neutralizing Titers at 1 Month after Dose 2 for
Participants Receiving Frozen -Liquid BNT162b2 with L NP
Size at Upper End of Specification or RTU BNT162b2 ................... 27
6.3.1.4. Fold Rises in Full -Length S -Binding IgG Levels From
Baseline Through 1 Month After Dose 2 for Participants
Receiving Frozen -Liquid BNT162b2 with LNP Size at Upper
End of Specification or RTU BNT162b2 ................................ .......... 28
6.4. Subset Analy ses................................ ................................ ................................ .......28
6.4.1. I mmunogenicity................................ ................................ .......................... 28
6.4.2. Safet y ................................ ................................ ................................ .......... 29
6.5. Baseline and Other Summaries and Anal yses................................ ......................... 29
6.5.1. Baseline Summaries ................................ ................................ .................... 29
6.5.1.1. Demographic Characteristics ................................ .................... 29
6.5.1.2. Medical History ................................ ................................ ......... 29
6.5.2. Study Conduct and Participant Disposition ................................ ................ 29
6.5.2.1. Participant Disposition ................................ .............................. 29
6.5.2.2. Blood Samples for Assay ................................ .......................... 29
6.5.2.3. E- Diaries ................................ ................................ .................... 30
6.5.3. Study Vaccination Exposure ................................ ................................ .......30
6.5.3.1. Vaccination Timing and Administration ................................ ...30
6.5.4. Prior/Concomitant Vaccinations and Concomitant Medications ............... 30
6.6. Safet y Summaries and Analyses ................................ ................................ ............. 30
7. INTERIM ANALYSES ................................ ................................ ................................ .......30
7.1. I ntroduction ................................ ................................ ................................ ............. 30
7.2. Analy sis Timings................................ ................................ ................................ .....30
8. REFERENCES ................................ ................................ ................................ .................... 31
LIST OF TABLES
Table 1. Summary of Changes ................................ ................................ .................. 6
Table 2. List of Primary and Secon dary Objectives, Endpoints, and
Estimands ................................ ................................ ................................ ....6
Table 3. Derived Variables for Presence of Each and An y Local Reaction
Within 7 Days for Each Dose ................................ ................................ ...10
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Page 5Table 4. Grading Scales for Local Reactions ................................ ......................... 11
Table 5. Grading Scales for Sy stemic Events ................................ ......................... 12
Table 6. Ranges for Fever ................................ ................................ ....................... 13
APPENDICES
Appendix 1. List of Abbreviations ................................ ................................ ........................... 32
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Page 82.2.Study Design
This is a Phase 3, randomized, observer- blind study to evaluate the safet y, tolerability , and
immunogenicit y of a lyophilized multiple formulation sof BNT162b2, an RNA -based
COVID -19 vaccine, administered on a 2 -dose schedule in healthy adults 18 through 55 y ears
of age. The study will be conducted in the United States with potential to expand to other
countries.
In Part 1, Pparticipants will receiv e either ly ophilized BNT162b2 in SDVs or frozen liquid
BNT162b2 in MDVs. Separately , lyophilized BNT162b2 presented in MDVs may also be
studied, where participants will receive either ly ophilized or frozen liquid BNT162b2 in
MDVs .Participants will be ran domized in a 1:1 ratio to 1 of the 2 groups (ly ophilized SDV
or frozen- liquid MDV control for ly ophilized SDV) .;if lyophilized MDV is studied ,
participants will be randomized in a 1:1 ratio to 1 of the 2 groups separately (l yophilized
MDV or frozen liquid MDV control for l yophilized MDV). Separatel y, in Part 2,
participants will be randomized in a 1:1 ratio to 1 of the 2 groups ( frozen -liquid BNT162b2
with L NP size at the upper end of specification or RTU BNT162b2 ).The duration of the
study for each part icipant will be approximately 2 months.
Approximately 275 550 participants will be randomly assigned to each 1oneof the 2two2 or
4 vaccine groups in Part 1 (ly ophilized SDV, frozen- liquid MDV control for ly ophilized
SDV , lyophilized MDV, or frozen liquid MDV control for ly ophilized MDV );,separatel y,
approximately 60 participants will be randomly assigned to 1oneof the 2twovaccine grou ps
in Part 2 (frozen- liquid BNT162b2 with LNP size at the upper end of specification or RTU
BNT162b2 )for a total of approximately 610 550or 1100 randomized participants. I t is
expected that approximately 488 440 or 880 evaluable participants will complete the study ,
based on a 20% nonevaluable rate.
Participants will receive 1 dose of study intervention as randomized at each vaccination visit
(Visits 1 and 2) separated by 21 day s in accordance with the study ’s SoA.
Blood samples will be collected at Visit 1 (Day 1/Vaccination 1) and Visit 3 (1 month after
Dose 2) to assess immunogenicity and to detect past SARS -CoV -2 infection. During the
same visits nasal swab samples will be collected to detect current SARS -CoV -2infection .
Participants will be observed for 30 minutes after eachvaccination and an y reactions
occurring during that time will be recorded as AEs. Local reactions, systemic events
(including fever), and use of antipy retic medication occurring within 7 day s after each
vaccination will be collected via a provided e -diary (or e -diary application). AEs and SAEs
will be collected from the signing of informed consent through and including Vis it3
(1month after Dose 2). In addition, any AEs occurring up to 48 hours after the blood draw
and nasal swab collection at Visit 3 must be recorded in the CRF.
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Page 93.ENDPOINTS AND BASELINE VARIAB LES: DEFINITIONS AND
CONVENTIONS
3.1.Primary Endpoints
3.1.1. Primary Immunogenicity Endpoints
Full-length S-b inding IgG levels at 1 month after Dose 2 for participants receiving
lyophilized formulation in SDVs orfrozen- liquid formulation in MDVs
Fulllength S b inding IgG levels at 1 month after Dose 2 for participants receiving
lyophilized formulation in M DVs orfrozen liquid formulation in MDVs
Concentrations of IgG levels will be determined in all participants at Visit 1 (Day 1) and
Visit 3 (1 month after Dose 2) using the SARS -CoV -2 full -length S- binding IgG -level assay .
Values below the LLOQ will be set to 0.5 × LLOQ forthe anal ysis. The LLOQ value for
full-length S-binding IgG will be included in the analy sis specification once it is available.
3.1.2. Primary Safety Endpoints
Local reactions ( pain at the injection site , redness, and swelling) within 7 days after each
dose
Systemic events (fever, fatigue , headache, chills, vomiting, diarrhea, new or worsened
muscle pain, and new or worsened joint pain )within 7 day s after each dose
AEs and SAEs from Dose 1 through 1 month after Dose 2
3.1.2.1. Local Reactions
The local reactions assessed and reported in the e -diary are pain at the injection site , redness,
and swelling, from Day 1 through Day 7 after each dose ,where Day 1 is the day ofeach
dose. This section describes derivations with details for the assessment of local reactions:
presence, severity level, duration, and onset day .
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Page 10Presence or Absence
For each local reaction and any local reaction on any day,Table 3define s the algorithm to
derive the presence of a reaction (y es or no) during the interval from Day 1 through Day 7,
where Day 1 is the day ofeach dose .
Table 3.Derived Variables for Presence of Each and Any Local Reaction Within
7Days forEach D ose
Variable Yes (1) No (0)
Presence of
each local reaction on
any dayParticipant reports thereaction
as“yes” onanyday
(Day 1through Day 7).Participant reports the reaction as “no” on
all7days (Day 1 through Day 7) or as a
combination of “no” and missing on
all7days (Day 1 through Day 7).
Presence of
anylocal reaction on
any dayParticipant reports any local reaction
as “yes” on any day (Day 1
through Day 7).For all 3 local reactions, participant reports
“no” on all 7days (Day 1 through Day 7) or
as a combination of “no” and missing on
all7days (Day 1 through Day 7).
Note: Missing e -diary data will not be imputed. Participants with no e- diary data reported will not be included
in the e -diary summaries.
Severity and Maximum Severity
Redness and swelling will be measured and recorded in measuring devic e units (range: 1 to
21)and then categorized during anal ysis as absent, mild, moderate, or severe based on the
grading scale inTable 4. Measuring device units can be converted to centimeters according
to the following scale: 1 measuring device unit = 0.5 cm. Pain at the injection site will be
assessed b y the participant as absent, mild, moderate, or severe according to the grading scale
inTable 4.
If a Grade 3 local reaction is reported in the reactogenicity e-diary , a telephone contact
should occur to ascertain further details and determine whether a site visit is clinically
indicated. Onl y an investigator or medicall y qualified person is able to classify a
participant’s local reaction as Grade 4. If a participant experiences a confirm ed Grade 4 local
reaction, the investigator must immediately notify Pfizer and, if it is determined to be related
to the administration of the study intervention, further vaccinations will be discontinued in
that participant.
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Page 11Table 4.Grading Scales for Local Reactions
Local Reaction Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4a)
Pain at the
injection siteDoes not interfere
with activityInterferes with
activityPrevents daily
activity Emergency room visit
or hospitalization for
severe pain
Redness >2.0 cm to 5.0 cm
(5 to 10 measuring
device units)>5.0 cm to 10.0 cm
(11 to 20 measuring
device units)>10cm
(≥21measuring
device units)Necrosis or exfoliative
dermatitis
Swelling >2.0 cm to 5.0 cm
(5 to 10 measuring
device units)>5.0 cm to 10.0 cm
(11 to 20 measuring
device units)>10cm
(≥21measuring
device units)Necrosis
a.Only an investigator or medically qualified person is able to classify a reaction as Grade 4; therefore ,a
confirmed Grade 4 should be reported as an AE in the case report form .
For each local reaction after each dose ,the maximum severity grade will be derived for the
e-diary collection period (Day 1 through Day 7, where Day 1 is the day ofeach dose ) as
follows:
maximum severity grade = highest grade (maximum severity ) within 7days after
vaccination (Day 1 through Day 7) among severity grades reported for that local
reaction in the e- diary .
Duration (First to Last Day Reported)
The duration (day s) of ea ch local reaction will be calculated as the number of day s from the
start of the first reported reaction to the resolution of the last reported reaction, inclusive.
Resolution is defined as the last day on which the reaction is recorded in the e-diary if the
reaction lasted 7days or less, or the day the reaction ended if it continued bey ond Day 7(the
latter will be collected on the CRF). If there is no known date when the reaction ended, then
duration will be missing (unknown). However, if a reaction i s ongoing atthe time of a
subsequent dose , the end date/day for the ongoing event would be the date/day that the next
dose is administered, which will be used for the duration computation. Participants with no
reported reaction have no duration.
Onset Day
The onset day of each local reaction will be derived. Onset day is defined as the first day of
reporting the reaction with any severit yafter vaccination .
For the onset day of each local reaction, if participants report a change in sev erity of the local
reaction, only the first day of reporting that specific local reaction will be counted.
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Page 123.1.2.2. Systemic Events (Systemic Event Symptoms and Fever)
The sy stemic events assessed and recorded in the e-diary arefever, fatigue , headache, chills,
vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain from
Day 1 through Day 7, where Day 1 is the day ofeach dose . The derivations for s ystemic
events will be handled similar lytothe way local reactions are handled for presence of event,
severit ylevel, duration, and onset day (see Section 3.1.2.1 ).Maximum temperature range
over the period from Day 1 through Day 7 will be map ped into the ranges described in
Table 6for summary of maximum temperature.
The sy stemic events w ill be assessed by the participant as absent, mild, moderate, or severe
according to the grading scale in Table 5.
If a Grade 3 s ystemic event is reported in the reactogenicity e-diary , a telephone contact
should occur to ascertain further details and determine whether a site visit is clinically
indicat ed. Only an investigator or medicall y qualified person is able to classify a
participant’s s ystemic event as Grade 4. If a participant experiences a confirmed Grade 4
systemic event, the investigator must immediately notify Pfizer and, if it is determine d to be
related to the administration of the study intervention, further vaccinations will be
discontinued in that participant.
Table 5.Grading Scales for Systemic Events
Systemic Event Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life Threatening
(Grade 4)
Fatigue Does not
interfere with
activitySome
interference with
activityPrevents daily
routine activityEmergency room visit or
hospitalization for severe
fatigue
Headache Does not
interfere with
activitySome
interference with
activityPrevents daily
routine activityEmergency room visit or
hospitalization for severe
headache
Chills Does not
interfere with
activitySome
interference with
activityPrevents daily
routine activityEmergency room vis it or
hospitalization for severe chills
Vom iting 1-2 times in
24hours>2 times in
24hoursRequires IV
hydrationEmergency room visit or
hospitalization for hypotensive
shock
Diarrhea 2 to 3 loose
stools in 24
hours4 to 5 loose
stools in
24hours6 or more loose
stools in 24 hoursEmergency room visit or
hospitalization for severe
diarrhea
New or w orsened
muscle painDoes not
interfere with
activitySome
interference with
activityPrevents daily
routine activityEmergency room visit or
hospitalization for severe new
or worsened muscle pain
New or w orsened
joint painDoes not
interfere with
activitySome
interference with
activityPrevents daily
routine activityEmergency room visit or
hospitalization for severe new
or worsened joint pain
Abbreviation: IV = intravenous.
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Page 13Oral temperature will be collected in the evening, daily , for 7 day s following each dose
(Day s 1 through 7, where Day 1 is the day of each dose) and at any time during the 7 days
that fever is suspected. Fever is defined as an oral temperature of ≥38.0°C (100.4°F). The
highest temperature for each day will be recorded in the e -diary .
Temperatures will be measured and recorded to 1 decimal place. Temperatures recorded in
degrees Fahrenheit will be programmatically converted to degre es Celsius first for reporting.
Temperatures <35.0 °Cand >42.0°C will be excluded from the anal ysis. Fever will be
grouped into ranges for the anal ysis according to Table 6.
If a fever of ≥39.0°C (102.1°F) is reported in the reactogenicity e-diary , a telephone contact
should occur to ascertain further details and determine whether a site visit is clinically
indicated. Onl y an investigator or medicall y qualified person is able to confirm a
participant’s fever as >40.0°C (>104.0°F). If a participant experiences a confirmed fever
>40.0°C (>104.0°F), the investigator must immediately notify Pfizer and, if it is determined
to be related to the administration of the study intervention, further vaccinations will be
discontinued in that participant.
Table 6.Ranges for Fever
≥38.0 -38.4° C (100.4 to 101.1°F)
>38.4 -38.9°C (101.2 to 102.0°F)
>38.9 -40.0°C (102.1 to 104.0°F)
>40.0°C (>104.0°F)
3.1.2.3. Use of Antipyretic Medication
The use of antip yretic medication is also recorded in the e -diary from Day 1 through Day 7,
where Day 1 is the day ofeach dose .For the use of antipy retic medication from Day 1
through Day 7after each dose , the following endpoints and variables will be derived for
analysis following the same rules as for local reactions (see Section 3.1.2.1 ), where
applicable.
Presence (y es or no) of use of antipy retic medication on each day (Day 1 through Day 7)
of each dose
Presence (y es or no) of use of antipy retic medicatio n on any day (Day 1 through Day 7)
of each dose
Duration (first to last day reported) o f use of antipy retic medication
Onset day of use of antipy retic medication
The use of antip yretic medication will be summarized and included in the systemic event
summary tables but wil l not be considered a s ystemic event.
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Page 143.1.2.4. Adverse Events
AEs will be assessed from the time of informed consent through and including up to 48 hours
after biospecimen collections at Visit 3 ( 1month after Dose 2 ). AEs will be categorized
according to MedDRA terms.
The primary endpoint “AEs from Dose 1 through 1 month after Dose 2”and other supportive
AE endpoints will be summarized bysystem organ class and preferred term at the participant
level.
This primary endpoint will be supported by summaries and listings of related AEs, severe
AEs, and immediate AEs (within the first 30 minutes after each dose ).
AE reporting will be based on the specific reporting period. Missing AE start dates will be
imputed following the Pfizer data standard rules as described in Section 5.3.
3.1.2.5. Serious Adverse Events
SAEs will also be collected from the time of informed consent through and including up to
48 hours after biospecimen collections at Visit 3 (1 month after Dose 2) . SAEs will be
categorized according to MedDRA terms.
The safet y endpoint “SAEs from Dose 1 through 1 month after Dose 2” will be summarized
by system organ class and preferred ter m at the participant level. Additionally , the SAEs will
be listed.
3.2.Secondary Endpoints
3.2.1. Secondary Immunogenicity Endpoints
Full-length S- binding IgG levels at baseline (before Dose 1) and 1 month after Dose 2 in
Part 1 only
Fold rises in full -length S-binding IgG levels from baseline (before Dose 1) through to
1month after Dose 2 in Part 1 only
3.3.ExploratoryOther Endpoints
3.3.Not applicable .
Full-length S- binding IgG levels and/or SARS-C0 oV-2 neutralizing titers at 1 month
after Dose 2 for participants receiving frozen- liquid BNT162b2 with LNP size at the
upper end of specification or,frozen- liquid BNT162b2 in MDVs , RTU BNT162b2 ,and
lyophilized formulation of BNT162b2 in S DVs
Full length S binding IgG levels and/or SARS C0 V2 neutralizing titers at 1 month after
Dose 2 for participants receiving RTU BNT162b2 orlyophilized formulation of
BNT162b2 in S DVs
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Page 15Full length S binding IgG levels and/or SARS C0V2 neutralizing titers at 1 month after
Dose 2 for participants receiving frozen liquid BNT162b2 with L NP size at the upper end
of specification or RTU BNT162b2
3.4.Baseline and Other Variables
Measurements or samples collected prior to Dose 1 are considered the baseline data for the
assessments.
3.4.1. Demographics , Medical History ,and Physical Examination
The demographic variables are age at Dose 1 (in years), sex (male or female), race
(black/African American, American Indian or Alaskan native, Asian, Native Hawaiian or
other Pacific Islander, white , multiracial, and not reported ), ethnicity (Hispanic/Latino,
non-Hispanic/non -Latino, and not reported ). In cases where more than 1 category is selected
for race, the participant would be counted und er the category “multiracial” for anal ysis.
Age at Dose 1 (in y ears) will be derived based on the participant’s birthday . For example, if
the vaccination day is 1 day before the participant’s 19 thbirthday , the participant is
considered to be 18 years old . For participant s who were randomized but not vaccinated, the
randomization date will be used in place of the date of Dose 1 for the age calculation. If the
randomization date is also missing, then the informed consent date will be used for theage
calculation.
Medical history will be categorized according to MedDRA.
If the clinical assessment indicates that a ph ysical examination is necessary to
comprehensivel y evaluate the participant atVisit 1 , a physical examination will be performed
and an y findings recorded in the source documents and, if clinicall y significant, it will be
recorded on the medical history CRF.
3.4.2. E- Diary Transmission
An e -diary will be considered transmitted if any data for the loca l reactions, sy stemic events,
or use of antip yretic medication are present for any day. If all data are missing for all the
items on the e -diary for all 7 day s after vaccination, then the e -diary will be considered not
transmitted.
3.4.3. Prior/Concomitant Vaccines and Concomitant Medications
The following concomitant medications and vaccinations will be recorded in the CRF:
All vaccinations received from 28 day s prior to study enrollment until the 1-m onth post–
Dose 2 visit (Visit 3).
Prohibited vaccines and medi cations listed in the protocol (Section 6.5.1 ) will be
recorded, to include start and stop dates, name of the medication, dose, unit, route, and
frequency .
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Page 16Prior and c oncomitant vaccines and concomitant medications will be coded using the WHO
Drug Dictiona ry.
3.5.Safety Endpoints
Local reactions, s ystemic events, AEs, and SAEs have been described above (Section 3.1.2 )
in the primary safety endpoints.
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Page 174.ANALYSIS SET S (POPULATIONS FOR ANAL YSIS )
Analy sis populations are define dfor the statistical anal ysis of safety and immunogenicit y
result sin the table be low. For the specified criteria in each population definition that are not
associated with unblinded information (randomized vaccine or vaccine actual lyreceived),
data for all participants will be assessed to determine if participants meet the criteria for
inclusion in each anal ysis population prior to unblinding and releasing the database for
analysis,andtheclassifications will be documented per standard operating procedures.
Population Description
Enrolled All participants who have a sign edICD.
Randomized All participants who are assigned a randomization number in the
IWR system.
Evaluable
immunogenicit y All participants who
1. a reeligible and random ized,
2.receive 2 doses of vaccine to which they are random ized,with
Dose 2 received wi thin the predefined window (19 to 42 days,
inclusive, after Dose 1) ,
3. have at least 1 valid and determinate immunogenicity result
within an appropriate window at1 month after Dose 2 ( 28to
42days, inclusive, after Dose 2),
4.are negative for both SARS- CoV -2 tests (RT- PCR and
N-binding antibody assay ) at both the Day 1 and 1 -month
post–Dose 2 visits , and
5.have no other important protocol deviations as determined by
the clinician .
All-available
immunogenicit yAll participants who receive at least 1 dose of the study
intervention and have at least 1 valid and determinate
immunogenicit y result after vaccination.
Safety All randomized participants who receive at least 1 dose of the
study intervention .
The important protocol deviations will be determined by the medical monitor. An important
protocol deviation is a protocol deviation that, in the opinion of Pfizer ’s clinician, would
materially affect assessment of immunogenicit y, eg, participant receipt of a prohibited
vaccine or medication that might affect immune response or a medication error with
suspected decrease in potency of the vaccine. Pfizer ’s clinician will identify those
participant s with important protocol deviations that result in exclusion fr om anal ysis
populations before an y unblinded anal ysis.
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Page 18For all the immunogenicity endpoints, the analy sis will be based on the evaluable
immunogenicit y population. An additional anal ysis will be performed based on the
all-available immunogenicity population if there is over 10% difference in sample size
between the all -available immunogenicit y population and the evaluable immunogenicit y
population. Participants will be summarized according to the vaccine group to which the y
were randomized.
The safet y analyses will be based on the safet y population. Participants will be summarized
by vaccine group according to the study interventions they actuall y received.
5.GENERAL METHODOLOGY AND CONVENTIONS
Methodology for summary and st atistical anal yses of the data collected in this study is
described here . The SAP may modify what is outlined in the protocol where appropriate;
however, an y major modifications of the primary endpoint definitions or their anal yses will
also be reflected in a protocol amendment.
The majority of Pfizer staff will be blinded to study intervention allocation. All laboratory
testing personnel performing serology assay s will remain blinded to study intervention
assigned/received throughout the study . Further details can be found in the protocol,
Section 6.3. The timing for statistical anal ysis is specified in Section 7.
5.1. Hypotheses and Decision Rules
5.1.1. Immunogenicity Hypotheses
The 2primary immunogenicity objective sisareto assess the noninferiority of the immune
response induced b y lyophilized SDV or MDV BNT162b2 compared to frozen- liquid MDV
BNT162b2. Taking the noninferiority assessment of ly ophilized SDV vs frozen liquid MDV
BNT162b2 as the example , tThe null hy pothesis (H0) is
H0: ln(μ 1) –ln(μ 2) ≤ ln(0.67) vs H 1: ln(μ 1) –ln(μ 2) > ln(0.67)
where ln(0.67) corresponds to a 1.5- fold margin for noninferiorit y and
ln(μ 1) is the natural log of the geometric mean of full- length S -binding IgG levels
measured 1 month after Dose 2 from participants receiving l yophilized SDV
BNT162b2;
ln(μ 2) is the natural log of the geometric mean of full- length S -binding IgG levels
measured 1 month a fter Dose 2 from participants receiving frozen -liquid MDV
BNT162b2 control for l yophilized SDV
Noninferiorit y will be declared if the lower bound of the 2 -sided 95% CI for the GMR of
lyophilized SDV relative to the corresponding frozen -liquid MDV control i s greater than
0.67 (1.5-fold criterion).
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Page 19The statistical hy pothesis and testing will be similar for the noninferiorit y assessment of
lyophilized MDV vs frozen liquid MDV BNT162b2.
5.1.2. Multiplicity Considerations
5.1.2. For assessment of the primary immunogenicity objectives regarding the
noninferiority of the immune response induced by lyophilized SDV or MDV BNT162b2
compared to frozen liquid MDV BNT162b2 , each hypothesis test will be carried out
separately at a significance level of 1sided 0.025. Each noninferio rity analysis
corresponds to a separate analysis of the respective lyophilized formulation and its
control, with a separate objective. The 2 lyophilized formulation groups and
corresponding control are included in the same study to improve operational eff iciency.
Therefore, there is no increase in the type I error rate, and no type I error adjustments
have been applied to the 2 noninferiority assessments.
There is onl y 1 h ypothesis for the primary immunogenicity endpoint, and within -group
descriptive summ aries will be provided for the secondary immunogenicity endpoint.
Consequently , no multiplicity adjustments are applied.
5.2.General Methods
5.2. Lypophilized SDV and MDV are 2 independent parts of the study. Data from the
lyophilized SDV and MDV parts of the study will be analyzed separately.
Unless stated otherwise, “vaccine group” in this section refers to participants receiving
lyophilized SDV, frozen- liquid MDV control for lyophilized SDV, lyophilized MDV, or
frozen liquid MDV control for ly ophilized MDV BNT162b2 .frozen -liquid BNT162b2 with
LNP size at the upper end of specification, or RTU BNT162b2 . CIs for all endpoints in the
statistical analy sis will be presented as 2- sided at the 95% level unless specified otherwise.
5.2.1. Analyses for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CI
where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the
Fdistribution (Clopper -Pearson ).1
5.2.2. Analyses for Continuous Data
Unless otherwis e stated, descriptive statistics for continuous variables are n, mean, median,
standard deviation, minimum, and maximum.
Continuous immunogen icity outcomes of IgG concentrations will be performed on the
natural log scale, and the results will be exponentia tedandreported in the original scale .
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Page 205.2.2.1. Geometric Mean Ratios
The GMRs will be calculated as the mean of the difference of logarithmically transformed
assay results between 2 vaccine groups and exponentiating the mean. Two-sided CI s will be
obtained by calculating CI s using Student’s t -distribution for the mean difference of the
logarithmicall y transformed assay results and exponentiating the confidence limits .
5.2.2.2. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the
logarithm transformation and then exponentiating the mean to express results on the original
scale. Two -sided 95% CIs will be obtained by taking log transforms of assay results,
calculating the 95% CI with reference to Student’s t- distribution, and then exponentiating the
confidence limits.
5.2.2.3. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results after vaccination to the results before vaccination.
GMFRs are limited to participants with nonmissing values at both time points.
GMFRs w ill be calculated as the mean of the difference of logarithmicall y transformed assay
results (later time point minus earlier time point) and exponentiating the mean. The
associated 2- sided 95% CI s will be obtained b y constructing CIs using Student’s
t-distribution for the mean difference on the logarithm scale and exponentiating the
confidence limits.
5.2.2.4. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participant s with values equal to or exceeding a
specified assay value versus the indicated assay value, for all observed assay values. Data
points will be joined by a step function with data points on the right side of the step.
5.3. Methods to Manage Missing Data
A partial AE start date (missing day ormissing both month and day ) will be imputed by
assigning the earliest possible start date using all available information, such as the stop date
of the AE and the vaccination date(s) from the same participant , following the Pfizer
standard of handling incomplete AE start date . Acomplete missing start date for an AE is
not allowed in the data collection.
The LLOQ for each assay will be provided by Vaccine Research and Development as part of
the electronic data transfer or within the Clinical Testing Completion Memo prior to
statisti cal analysis. Assay results above the LLOQ will be reported, and values below the
LLOQ, denoted as BLQ, will be imputed as 0.5 × LLOQ for anal ysis.
No additional imputation will be applied to other missing data.
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Page 216.ANALYSES AND SUMMARIES
6.1.Primary Endpoints
6.1.1. Primary Immunogenicity Endpoint s
6.1.1.1. Full-Length S -Binding IgG Concentrations at 1 Month After Dose 2for
Participants Receiving L yophilized Formulation in SDVs or Frozen -Liquid
Formulation in MDVs
6.1.1.1.1. Main Analysis
Estimand: GMR from of lyophilized formulation in SDVs to frozen- liquid formulation in
MDVs (Section 2.1).
Analy sis set: E valuable immunogenicit ypopulation , all-available immunogenicity
population (as applicable) (Section 4).
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : The GMR and co rresponding 95% CI will be calculated using the
method described in Section 5.2.2.1 .The noninferiority will be assessed b y comparing
the lower limit of the 95% CI against the noninferiority criterion (Section 5.1.1 ).
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The observed GMC sand 95% CI s for IgG concentr ation will be
presented for lyophilized SDV and frozen -liquid MDV . The GMR for the comparison
and the corresponding 95% CI will be calculated .
6.1.1.2. Full Length S Binding IgG Concentrations at 1 M onth After Dose 2for
Participants Receiving L yophilized Formulation in M DVs or Frozen Liquid
Formulation in MDVs
6.1.1.2.1. Main Analysis
Estimand: GMR from ly ophilized formulation in MDVs to frozen liquid formulation in
MDVs (Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all available immunogenicity
population (as applicable) ( Section 4).
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : The GMR and corresponding 95% CI will be calculated using the
method described in Section 5.2.2.1 .The noninferiority will be assessed b y comparing
the lower limit of the 95% CI against the noninferiority criterion (Section 5.1.1 ).
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Page 22Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The observed GMC sand 95% CI sfor IgG concentration will be
presented for ly ophilized MDV and frozen liquid MDV . The GMR for the comparison
and corresponding 95% CI will be calculated .
6.1.2. Primary Safety Endpoints
6.1.2.1. Local Reactions
6.1.2.1.1. Main Analysis
Estimand: The percentage of participants reporting prompted local reactions ( pain at the
injection site , redness, and swelling) within 7 days after each dose (Section 2.1 ).
Analy sis set: S afety population (Section 4).
Analy sis time point: Within 7days after each dose .
Analy sis methodology : Descriptive statistics (Section 5.2.1 ).
Intercurrent events and missing data: The participants without any e-diary data
throughout the 7 day s after vaccination will be excluded from the anal ysis at that
particular vaccination; missing values will not be imputed. Confirmed e -diary errors will
be excluded from the analy sis.
Reporting results: Proportion of participants reporting each local reaction after each dose
will be summarized by maximum severity level and cumulatively across severity level s.
The percentage (%), the numerator (n) and denominator (N) used in the percentage
calcu lation, and the corresponding 95% 2-sided Clopper -Pearson CI will be pr esented for
each vaccine group.
6.1.2.1.2. Supplementary Analyses
As supplementary analy ses to support the assessment of local reactions, the following
endpoints (as defined in Section 3.1.2.1 ) will be summarized with the same anal ysis time
point and anal ysis population:
Duration (day s) of each local reaction after each dose .
Onset day of each local reaction after each dose .
These continuous endpoints will be summarized by display ing n, mean, median, standard
deviation, minimum, and maximum for each vaccine group.
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Page 23In addition, the proportions of participants reporting each prompted local reaction after an y
dose will be summari zed by maximum severity level.
Figures:
Bar charts with the proportions of participants for each local reaction on each day (Day 1
through Day 7)and any day (Day 1 through Day 7)will be plotted for each vaccine group
after each dose , with different patterns display edin the bar charts for different severit y levels
(each day ) and different maximum severity levels for an y day,respectivel y.
6.1.2.2. Systemic Events
6.1.2.2.1. Main Analysis
Estimand: The percentage of participants reporting s ystemic events (fever, fatigue,
headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened
joint pain) within 7 day s after each dose (Section 2.1 ).
Analy sisset: S afety population (Section 4).
Analy sis time point: Within 7days after each dose.
Analy sis methodology : Descriptive statistics (Section 5.2.1 ).
Intercurrent events and missing data: The participants without any e-diary data
throughout the 7 day s after vaccination will be excluded from the anal ysis at that
particular vaccination; missing values will not be imputed. Confirmed e -diary errors will
be excluded from the analy sis.
Reporting results: Proportion of participants repor ting each s ystemic event after each
dose will be summarized by maximum severity level and cumulativel y across severity
levels . The percentage (%), the numerator (n) and denominator (N) used in the
percentage calculation, and the corresponding 95% 2-sided Clopper -Pearson CI will be
presented for each vaccine group.
6.1.2.2.2. Supplementary Analyses
As supplementary analy ses to support the assessment of systemic events , the following
endpoints ( as defined in Section 3.1.2.2 ) will be summarized with the same anal ysis time
point andanalysis population :
Duration of each s ystemic event after each dose .
Onset day of each s ystemic event after each dose .
These continuous endpoints will be summarized by display ing n, mean, median, standard
deviation, minimum, and maximum for each vaccine group.
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Page 24The use of antip yretic medication (see Section 3.1.2.3 ) will be summarized similarly to
systemic events, except that there is no severity level associated with the use of antipy retic
medication.
In addition, the proportions of participants reporting each prompted systemic event after an y
dose will be summarized by maximum severity level.
Figures:
Bar charts with the proportions of participants for each s ystemic event on each day (Day 1
through Day 7) and an y day (Day 1 through Day 7) will be plotted for each vaccine group
after each dose, with different patterns display ed in the bar charts for different severit y levels
(each day ) and different maximum severity levels for an y day,respectivel y.
6.1.2.3. Adve rse Events
6.1.2.3.1. Main Analysis
Estimand : The percentages of participants reporting AEs from Dose 1through 1 month
after Dose 2 ( Section 2.1).
Analy sis set: Safety population ( Section 4).
Analy sis time point : Dose 1 through 1 month after Dose 2.
Analy sis methodology : Descriptive statistics described in Section 5.2.1 .
Intercurrent events and missing data: Nomissing values will be imput edexcept for
partial AE start dates (Section 5.3).
Reporting result s: The numerator (n) and the denominator (N) used in the percentage
calculation, the percentage (%), and the corresponding 2 -sided 95% Clopper -Pearson CI
for participants reporting any AE, by each s ystem organ class and each preferred term
within sy stem organ class, will be presented for each vaccine group.
6.1.2.3.2. Supplementary Analyses
As supplementary analy ses to support the interpretation of the main analysisresults ,
descriptive summary statistics will also be provided by vaccine group for related AEs and
severe AEs , each from Dose 1 through 1 month after Dose 2. Immediate AEs (within the
first 30 minutes after each dose ) will also be summarized for each vaccine group , if the
number of immediate AEs is sufficient lylarge ;otherwise ,they will be listed only .
AEs that occur redafter informed consent and before Dose 1 will not be included in the AE
summar ytables , but will be included in the AE listings.
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Page 256.1.2.4. Ser ious Adverse Events
6.1.2.4.1. Main Analyses
Estimand: The percentage of participants reporting SAEs from Dose 1 through 1 month
after Dose 2 (Section 2.1).
Analy sis set: Safety population (Section 4).
Analy sis time point: Dose 1 through 1 month after Dose 2.
Analy sis methodology : Descriptive statistics .
Reporting results: The numerator (n) and the denominator (N) used in the percentage
calculation, the percentage (%), and the corresponding 2 -sided 95% Clopper -Pearson CI
for participants reporting any SAEs, by each s ystem organ class and each preferred term
within sy stem organ class, will be presented for each vaccine group.
6.2.Secondary En dpoints
6.2.1. Immunogenicity Endpoint s
6.2.1.1. Full-Length S-B inding IgG Levels in Participants Receiving Lyophilized
BNT162b2 in SDVs or Frozen -Liquid BNT162b2 in MDVs
6.2.1.1.1. Main Analyses
Estimand: GMCs (Section 2.1).
Analysis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicable) (Section 4).
Analy sis time point s: Baseline (before Dose 1) and 1 month after Dose 2.
Analy sis methodology : Descriptive statistics .
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The GMC sand corresponding 2- sided 95% CIs for baseline and
1month after Dose 2 will be presented for each vaccine group .
Figures:
Empiri cal RCDCs will be presented for the IgG concentrations for each vaccine group . The
32vaccine groups will be display ed in 1figure. The figure w illdisplay 4 curves, one for
baseline (Day 1) and one for 1 month after Dose 2, for each of the vaccine groups . Only the
evaluable immunogenicity population will be used.
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Page 266.2.1.2. Fold Rise sin Full-Length S-B inding IgG Levels F rom Baseline Through
1Month After Dose 2 in Participants Receiving Lyophilized BNT162b2 in SDVs or
Frozen -Liquid BNT162b2 in MDVs
Estimand: GMFRs (Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicab le) (Section 4).
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : Descriptive statistics.
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The GMFRs at 1 month after Dose 2 and corresponding 2- sided 95%
CIs will be prese nted for each vaccine group.
6.3.Other Endpoints
Not applicable .
6.3.1. Exploratory Endpoints
6.3.1.1. Full-Length S -Binding IgG Concentrations and/or SARS -CoV2 Neutralizing
Titers at 1 Month after Dose 2 for Participants Receiving Frozen -Liquid BNT162b2
with LNP Size at Upper End of Specification or Frozen -Liquid BNT162b2 in MDVs
Estimand: GMR from offrozen- liquid BNT162b2 with L NP size at upper end of
specification relative tofrozen -liquid BNT162b2 in MDVs (Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicable) ( Section 4)for participants without evidence of SARS CoV2
infection during the study .
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : The GMR and corresponding 95% CI will be calculated using the
method described in Section 5.2.2.1 . The noninferiority will be assessed b y comparing
the lower limit of the 95% CI against the noninferiority criterion ( Section 5.1.1 ).A
random sample of 30 participants receiving frozen- liquid BNT162b2 in MDVs will be
selected from Part 1 of the study for this anal ysis.
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
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Page 27Reporting resul ts: The observed GMCs for IgG concentration and/or GMTs for SARS -
CoV -2 neutralizing titers and 95% CIs for IgG concentration will be presented for frozen-
liquid BNT162b2 with LNP size at upper end of specification and frozen -liquid
BNT162b2 in MDVs . The GMR for the comparison and the corresponding 95% CI will
be calculated.
6.3.1.2. Full-Length S -Binding IgG Concentrations and/or SARS -CoV2 Neutralizing
Titers at 1 Month after Dose 2 for Participants Receiving RTU BNT162b2 or
Lyophilized BNT162b2 in SDVs
Estimand: GMR from ofRTU BNT162b2 relative tolyophilized BNT162b2 in SDVs
(Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicable) ( Section 4)for participants without evidence of SARS CoV2
infection during the study .
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : The GMR and corresponding 95% CI will be calcula ted using the
method described in Section 5.2.2.1 . The noninferiority will be assessed b y comparing
the lower limit of the 95% CI against the noninferiority criterion ( Section 5.1.1 ).A
random sample of 30 participants receiving frozen liquid lyophilized BNT162b2 in
MSDVs will be selected from Part 1 of the stud y for this analysis.
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The observed GMCs for IgG concentratio ns and/or GMTs for SARS -
CoV -2 neutralizing titers and 95% CIs for IgG concentration will be presented for RTU
BNT162b2 and lyophilized BNT162b2 in SDVs. The GMR for the comparison and the
corresponding 95% CI will be calculated.
6.3.1.3. Full-Length S -Binding IgG Concentrations and/or SARS -CoV2 Neutralizing
Titer s at 1 Month after Dose 2 for Participants Receiving Frozen -Liquid BNT162b2
with LNP Size at Upper End of Specification or RTU BNT162b2
Estimand: GMCs and/or GMTs (Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicable) (Section 4).
Analy sis time point s: Baseline (before Dose 1) and 1 month after Dose 2.
Analy sis methodology : Descriptive statistics .
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Page 28Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The GMC sand/or GMTs and the corresponding 2- sided 95% CI s for
baseline and 1 month after Dose 2 will be presented for each vaccine group.
Figures:
Empirical RCDCs will be presented for the IgG concentrations and/or SARS- CoV -2
neutralizing titers for each vaccine group. The 32vaccine groups will be display ed in 1
figure. The figure will display 4 curves, one for baseline (Day 1) and one f or 1 month after
Dose 2, for each of the vaccine groups. Only the evaluable immunogenicity population will
be used.
6.3.1.4. Fold Rises in Full -Length S -Binding IgG Levels From Baseline Through
1Month After Dose 2 for Participants Receiving Frozen- Liquid BNT162b2 with LNP
Size at Upper End of Specification or RTU BNT162b2
Estimand: GMFRs ( Section 2.1).
Analy sis set: Evaluable immunogenicit y population, all- available immunogenicity
population (as applicable) ( Section 4).
Analy sis time point: 1 Month after Dose 2.
Analy sis methodology : Descriptive statistics.
Intercurrent events and missing data: Serology data deemed unevaluable because of
noncompliance with the key protocol criteria will be excluded. Missing data will not be
imputed.
Reporting results: The GMFRs at 1 month after Dose 2 and corresponding 2- sided 95%
CIs will be presented for each vaccine group.
6.4.Subset Analyses
Subgroup ana lyses by sex (male and female) and race (white, African American, and others
[the rest combined]) will be performed for the following immunogenicit yand safet y
endpoints for Part 1 of the study .
6.4.1. Immunogenicity
GMCs of full -length S -binding IgG concentrations and associated 2 -sided 95% CI s at
baseline and 1 month after Dose 2 will be summarized by vaccine group for each subgroup.
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Descriptive summary statistics for the following endpoints will be provided by vaccine group
for each subgroup.
Proport ion of participants reporting local reactions, by maximum severity level.
Proport ion of participants reporting sy stemic events, by maximum severity level.
Proportion of participants reporting AE swithin 1 month after Do se 2,by system organ
class and preferred term.
6.5.Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
6.5.1.1. Demographic Characteristics
Demographic characteristics ,including age at Dose 1, sex, race, and ethnicity ,willbe
summarized using descriptive st atistics for each vaccine group and overall. The summary
will be provided for the safet y population and the evaluable immunogenicity population .
6.5.1.2. Medical History
Each reported medical history term will be mapped to a sy stem organ class and preferred
term a ccording to the current version (at the time of reporting) of MedDRA. The number
and percentage of participant s with at least 1 diagnosis, overall and at each sy stem organ
class and preferred term level, will be summarized by vaccine group and overall forthe
safet y population .
6.5.2. Study Conduct and Participant Disposition
6.5.2.1. Participant Disposition
The number and percentage of randomized participant s will be included in the participant
disposition summary . In addition, the number s and percentages of participants who received
vaccination s(Dose s 1and2),who completed the study , and w ho withdrew from the study ,
along with the reasons for withdrawal ,will be tabulated by vaccine group (according to
randomized group assignment) and overall . The reasons for withdr awal will be those as
specified in the database.
Randomized p articipant s excluded from the safety or immunogenicit y analysis population s
will also be summarized separately , along with the reasons for exclusion ,by vaccine group.
6.5.2.2. Blood Samples for Assay
The number and percentage of randomized participant s providing blood samples within and
outside of protocol -prespecified time frames will be tabulated separatel y forbaseline (before
Dose 1) and 1 month after Dose 2.
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Page 306.5.2.3. E-D iaries
The number and percentage of vaccinated participants not transmitting the e- diary ,
transmitting the e -diary for each day , and transmitting the e-diary for alldays in the required
reporting period for each dose will be summarized according to the vaccine actuall y received .
The s afety population will be used.
6.5.3. Study Vaccination Exposure
6.5.3.1. Vaccination Timing and Administration
For each dose, t he number and percentage of participants randomized and receiving each
study intervention within the protocol- specified ti me frame , as well as before and after the
specified time frame ,will be tabulated for each vaccine group and overall for all randomized
participant s. The denominator for the percentage calculation s is the total number of
randomized participant s in the given vaccine group or overall.
A listing of participant s who received a vaccine other than that which they were randomized
to receive will be produced, if an y such incorrect dosing occurs .
A listing of participant s showing the randomized vaccine and the v accine actually received at
each dosewill be presented.
6.5.4. Prior/Concomitant Vaccination sand Concomitant Medications
Each prior/concomitant vaccine will be summarized according to the ATC fourth -level
classification. Allvaccine sreceived within 28 days before Dose 1 will be listed. The
number and percentage of participant s receiving each concomitant vaccine after Dose 1 of
study intervention will be tabulated for each vaccine group for all participants in the safety
population . Similar s ummarization will be done separately forconcomitant medications
received.
6.6. Safety Summaries and Analyses
Summaries and anal yses of the safet y measures , local reactions, sy stemic events, AEs, and
SAEs ,are described under the Primary Safet y Endpoints (see Section 6.1.2 ).
7. INTERIM ANALYSES
7.1.Introduction
No interim anal ysis is planned in this study . A program -wide EDMC will monitor the safet y
data for this study .
7.2.Analysis Timings
7.2. Statistical analy ses will be carried out when the final data for specified objectives for
a given study part are available while the study is ongoing .
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Page 31Statistical analy ses will be carried out when the final data for specified o bjectives for a given
study part are available while the study is ongoing .The l yophilized SDV and MDV
BNT162b2 are 2 independent parts of the stud y. Data from these 2 parts of the study will be
analyzed separatel y. Statistical anal yses will be carried out when the final data for a given
part are available.
8.REFERENCES
1Collett D. Statistical inference for binary data. In: Modelling binary data .London,
England: Chapman & Hall; 1991: 17-42.
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Page 32Appendix 1.List of Abbreviations
Abbreviation Term
AE adverse event
ATC Anatomic Therapeutic C hemical
BLQ below the limit of quantitation
CI confidence interval
COVID -19 coronavirus disease 2019
CRF case report form
e-diary electronic diary
EDMC external data monitoring committee
GMC geometric mean concentration
GMFR geometric mean fold rise
GMR geometric mean ratio
GMT geometric mean titer
ICD informed consent document
IgG immunoglobulin G
IWR interactive Web -based response
LLOQ lower limit of quantitation
LNP lipid nanoparticle
MDV multidose vial
MedDRA Medical Dictionary for Regulatory Activities
N SARS -CoV -2 nucleoprotein
N/A not applicable
RCDC reverse cumulative distribution curve
RNA ribonucleic acid
RTU ready-to-use
RT-PCR reverse transcription– polymerase chain reaction
S spike protein
SDV single -dose vial
SAE serious adverse event
SARS -CoV -2 severe acute respiratory syndrome coronavirus 2
SAP statistical analy sis plan
SoA schedule of activities
WHO World Health Organization
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