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1HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TRUMENBA safely and effectively. See full p rescribing information for
TRUMENBA .
TRUMENBA®(Meningococcal Group B Vaccine )
Suspension for intramuscular injection
Initial U.S. Approval: 2014
------------------------ ----INDICATIONS AND USAGE ---------------------------
Trumenba is indicated for active immunization to prevent invasive disease
caused by Neisseria meningitidis serogroup B .Trumenba is approved for
use in individuals 10 through 25 years of age .(1)
The effectiveness of thetwo-dose schedule of Trumenba against diverse
N.meningitidis serogroup B strains has not been confirmed. (1)
-------------- --------- ----DOSAGE AND ADMINISTRATION -------------------
For intramuscular use only .(2)
Three -dose schedule: Administer a dose (0.5 mL) at 0, 1-2 , and
6month s.(2.1)
Two -dose schedule: Administer a dose (0.5 mL) at 0and 6 month s.
If the second dose is administered earlier than 6 months after the first
dose, a third dose should be administered at least 4 months after the
second dose. (2.1)
---------------------------- DOSAGE FORMS AND STRENGTHS ----------------------
Suspension for intr amuscular injection in 0.5 mL single -dose prefilled
syringe .(3)------------------------------------ CONTRAINDICATIONS ---------------------------------
Severe allergic reaction after a previous dose of Trumenba .(4)
----------------------- WARNINGS AND PRECAUTIONS -----------------------
Syncope (fa inting) can occur in association with administration of injectable
vaccines, including Trumenba. Procedures should be in place to avoid injury
from fainting. (5.4)
---------------------------------- ADVERSE REACTIONS ------------------------------------
Themost common solicited adverse reactions in adolescents and young adults
were pain at the injection site ( ≥85%), fatigue (≥60%), headache (≥55%), and
muscle pain ( ≥35%). (6)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer ,Inc.
at 1-800-438- 1985 orVAERS at 1 -800-822-7967 or http://vaers.hhs.gov .
------------------------------- USE IN SPECIFIC POPULATIONS -----------------------
Pediatric Use: Safety and effectiveness have not been established in
children <10 years of age. I n a clinical study, 90% of infants <12 months
of age who were vaccinated with a reduced dosage formulation had
fever .(8.4)
See 17 for PATIENT COUNSELING INFORMATION
Revised: 8/2019
_______________________________________________________ ________________________________________________________________________________
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dose and Schedule
2.2Administration
2.3 Use of Trumenba with other Meningococc al Group B Vaccines
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Management of Allergic Reactions
5.2 Altered I mmunocompetence
5.3 Limitation of Vaccine Effectiveness
5.4 Syncope
6 ADVERSE REACTIONS
6.1 Clinical Trial sExperience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy8.2Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
14 CLINICAL STUDIES
14.1 Immunogenicity
14.2 Concomitant Vaccine Administration
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.
_____________________________________________________________________________________________________________________________ __________
FDA-CBER-2021-5683-0951380
2FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Trumenba is indicated for active immunization to prevent invasive disease caused b y Neisseria meningitidis
serogroup B .Trumenba is approved for use in individuals 10 through 25 yearsof age .
The effectiveness of the two -dose schedule of Trumenba against diverse N. meningitidis serogrou pB strains has
not been confirmed .
2 DOSAGE AND ADMINISTRATION
For intramuscular use only .
2.1 Dose and Schedule
Three -dose schedule: Administer a dose (0.5 mL ) at 0, 1-2,and 6 month s.
Two -dose schedule :Administer a dose (0.5 mL) at 0 and 6 month s.If the second dose is administered earlier
than 6 months after the first dose, a third dose should be administered at least 4 months after the second dose.
The choice of dosing schedule may depend on the risk of exposure and the patient’s susceptibili ty to
meningococcal serogroup B disease .
2.2 Administration
Shake sy ringe vigorousl y to ensure that a homogenous white suspension of Trumenba is obtained. Do not use
the vaccine if it cannot be re -suspended. Parenteral drug products should be inspected vi suall y for particulate
matter and discoloration prior to administration, whenever solution and container permit. Do not use if
particulate matter or discoloration is found.
Inject each 0.5 mL dose intramuscularl y, using a sterile needle attached to the s upplied prefilled s yringe. The
preferred site for injection is the de ltoid muscle of the upper arm. Do not mix Trumenba with any other vaccine
in the same syringe.
2.3 Use of Trumenba with other Meningococcal Group B Vaccines
Sufficient data are not avail able on the safet y and effectiveness of using Trumenba and other meningococcal
group B vaccines interchangeabl y to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
Trumenba is a s uspension for intramuscular injection in 0.5 mL single-dose pr efilled s yringe.
4 CONTRAINDICATIONS
Severe allergic reaction after a previous dose of Trumenba .
FDA-CBER-2021-5683-0951381
35 WARNINGS AND PRECAUTIONS
5.1 Management of Allergic Reactions
Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediatel y
available should an acute anaph ylactic reaction occur following administration of Trumenba.
5.2 Altered Immunocompetence
Reduced Immune Response
Some individuals with altered immunocompetence may have reduced immune responses to Trumenba.
Complement Deficiency
Persons with certain complement deficiencies and persons receiving treatment that inhibits terminal
complement activation (for example, eculizumab) are at increased risk for invasive disease caused by N.
meningitidis serogroup B even if they develop antibodies following vaccination with Trumenba [see Clinical
Pharmacology (12.0)].
5.3 Limitation of Vaccine Effectiveness
As with any vaccine, vaccination with Trumenba may not protect all vaccine recipients against N. meningitidis
serogroup B infections.
5.4 Syncope
Syncope (fainting) can occur in association with administration of injectable vaccines, including Trumenba.
Procedures should be in place to avoid injury from fainting.
6 ADVERSE REACTIONS
In clinical studies, the most co mmon solicited adverse reactions in adolescents and young adults were pain at
the injection site ( ≥85%), fatigue (≥60%), headache (≥55%), and muscle pain (≥35%). Nausea was reported in
up to 24% of adolescents in earl y phase studies.
6.1 Clinical Trial sExperience
Because clinical trials are conducted under widely vary ing conditions, adverse reaction rates observed in the
clinical trials of a vaccine cannot be directl y compared to rates in the clinical trials of another vaccine and may
not reflect the rates observed in clinical practice .
The safet y of Trumenba was evaluated in 15,227 subjects 10through 25 years of age in 11 clinical studies
(8 randomized controlled and 3 supportive non- controlled studies) conducted in the U .S., Europe, Canada,
Chile ,and A ustralia. A total of 11,333 adolescents (10through 18 years of age) and 3,894 adults (19 through
25years of age) received at least one dose of Trumenba. A total of 5,501 subjects 10through 25 years of age in
the control groups received saline placebo an d/or one of the following vaccine (s): Human Papillomavirus
Quadrivalent (Ty pes 6, 11, 16, and 18) Vaccine, Recombinant ( HPV4 ) (Merck & Co ., Inc.); Tetanus Toxoid,
Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) (Sanofi Pasteur L td.);
Meningococcal Poly saccharide (Serogroups A, C, Y and W -135) Diphtheria Toxoid Conjugate Vaccine
FDA-CBER-2021-5683-0951382
4(MCV4) (Sanofi Pasteur Inc.) ; a non -U.S.licensed reduced diphtheria toxoid, tetanus toxoid, acellular pertussis
and inactivated polio virus vaccine (dTaP-IPV)(Sanofi Pasteur ,Inc.); Hepatitis A Vaccine , Inactivated (HAV)
(GlaxoSmithKline Biologicals ).
The safet y evaluation in the clinical studies included an assessment of: (1) solicited local and s ystemic
reactions, and use of antipy retic medication after each vaccination in an electronic diary maintained by the
subject or the subject’s parent/legal guardian and (2) spontaneous reports of adverse events (AEs), including
serious adverse events (SAEs), throughout the study (day of vaccination through one mont h or 6 months after
the last vaccination, depending on the stud y and safety parameter).
In controlled studies, demographic characteristics were generally similar with regard to gender, race, and
ethnicity among subjects who received Trumenba and those who received control. Overall, across the
11 studies, among the subjects who received Trumenba, 50.5 % were male and 49.5% were female, and the
majority were White ( 86.3%) and non -Hispanic/non -Latino ( 87.3%).
Solicited Local and Systemic Adverse Reaction s
Study 1was a Phase 3, randomized, active -controlled, observer -blinded, multicenter trial in the U.S., Canada ,
and Europe in which 2,693 subjects 10 to 18 y ears of age receive d at least 1 dose of Trumenba on a 0 -, 2-,
and6-month schedule . A control group (n=897) received HAV at 0 and 6 months and saline at 2 months.
87.3% of subjects were White, 8.1% were Black or African -American, 0.4 % were Asian, and 5.8% were
Hispanic or Latino. Overall, 51.5% of subjects were male , 55.6% of participants were 1 0to14 years age, and
44.4% were 15 to 18 y ears of age.
Study 2 was a Phase 3, randomized, placebo -controlled, observer -blinded, multicenter trial in the U.S. , Canada ,
and Europe in which 2,471 subjects 18 to 25 y ears of age received at least 1 dose of Trumenba and 822 subjects
received saline on a 0-, 2,-and6-month schedule . 76.1% of subjects were White, 20.8% were Black or
African -American, 1.6% were Asian, and 17.1% were Hispanic or Latino. Overall, 41.3% of subjects were
male.
Local adverse reactions at the Trumenba injection site and control (HAV/saline or saline) injection site were
assessed in both studies.
Table s 1and 2 present the percentage and severity of reported local adverse reactions within 7 days following
each dose of Trumenba or control (HAV /saline or saline) for Study 1 and Study 2, respectivel y.
Local adverse reactions were reported more frequently following Trumenba compared to control (see Table s 1
and 2 ).
Table 1: Percentages of Subjects 10 to 18 Years of Age (Study 1a) Reporting Loc al Adverse Reactions Within
7Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabHAV/SalinebTrumenbabHAV/SalinebTrumenbabHAV/Salineb
Local
ReactionN=2681 N=890 N=2545 N=843 N=2421 N=821
Painc
Anyd86.7 47.0 77.7 15.2 76.0 34.0
Mild 41.1 36.5 39.4 12.3 34.1 23.8
Moderate 40.7 9.9 33.2 2.7 36.5 9.9
Severe 5.0 0.6 5.1 0.1 5.4 0.4
Rednesse
FDA-CBER-2021-5683-0951383
5Table 1: Percentages of Subjects 10 to 18 Years of Age (Study 1a) Reporting Loc al Adverse Reactions Within
7Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabHAV/SalinebTrumenbabHAV/SalinebTrumenbabHAV/Salineb
Anyd16.2 1.3 12.5 0.6 13.9 1.1
Mild 5.6 1.2 5.2 0.6 4.9 1.0
Moderate 8.8 0.1 6.1 0.0 6.8 0.1
Severe 1.9 0.0 1.1 0.0 2.2 0.0
Swellinge
Anyd18.0 2.2 13.9 0.6 15.4 0.9
Mild 8.5 1.8 6.3 0.5 7.9 0.7
Moderate 8.8 0.4 7.3 0.1 6.8 0.1
Severe 0.7 0.0 0.2 0.0 0.7 0.0
aStudy 1: National Clinical Trial (NCT) number NCT01830855.
bTrumenba was administered at 0, 2, and 6 months. HAV wa s administered at 0 and 6 months and saline was administered at 2 months.
cMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
d"Any" is defined as the cumulative frequency of subjects who repor ted a reaction as "mild", "moderate", or "severe" within 7 days of
vaccination.
eMild (2.5 -5.0 cm); moderate ( >5.0-10.0 cm); severe (>10.0 cm).
Table 2: Percentages of Subjects 18 to 25 Years of Age (Study 2a) Reporting Local Adverse Reactions Within
7Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabSalinebTrumenbabSalinebTrumenbabSalineb
Local
ReactionN=2425 N=798 N=2076 N=706 N=1823 N=624
Painc
Anyd84.2 11.8 79.3 7.8 80.4 6.7
Mild 42.3 10.7 42.2 6.8 36.1 6.4
Moderate 37.1 1.1 32.7 1.0 38.9 0.3
Severe 4.8 0.0 4.4 0.0 5.3 0.0
Rednesse
Anyd13.8 0.6 11.8 0.3 17.1 0.2
Mild 5.8 0.5 4.6 0.1 6.2 0.2
Moderate 7.1 0.0 6.3 0.0 8.6 0.0
Severe 0.9 0.1 0.9 0.1 2.3 0.0
Swellinge
Anyd15.5 0.6 14.0 0.4 16.6 0.3
Mild 8.5 0.3 7.7 0.3 8.8 0.0
Moderate 6.8 0.3 6.0 0.1 7.2 0.3
Severe 0.2 0.1 0.3 0.0 0.5 0.0
aStudy 2: National Clinical Trial (NCT) number NCT01352845.
bTrumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
cMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
d"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of
vaccination.
eMild (2.5 -5.0 cm); moderate ( >5.0-10.0 cm); severe (>10.0 cm).
In Stud y 1, mean duration of pain was 2.4 to 2.6 days (range 1 -17 day s), for redness 2.0 to 2.2 day s (range
1-12days) and for swelling 2.0 to 2.1 day s (range 1 -21 day s) in the combined Tr umenba group. In Study 2,
mean duration of pain was 2.6 to 2.8 day s (range 1 -67 day s), for redness 2.2 to 2.5 day s (range 1 -13 day s) and
for swelling 2.1 to 2.6 day s (range 1 -70 day s) in the Trumenba group.
Table s3 and 4 present the percentage and severi ty of reported solicited systemic adverse reactions within
FDA-CBER-2021-5683-0951384
67daysof each dose of Trumenba or control (HAV/saline or saline) for Study 1 and Study 2, respectively .
Table 3: Percentages of Subjects 10 to 18 Years of Age (Study 1a) Reporting Systemic Advers e Reactions and Use
of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabHAV/SalinebTrumenbabHAV/SalinebTrumenbabHAV/Salineb
Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
Fever ( ≥38°C)c
≥38.0°C 6.4 1.9 2.0 1.5 2.7 2.3
38.0°C to <38.5°C 4.0 1.3 1.2 0.7 1.8 1.3
38.5°C to <39.0°C 1.9 0.3 0.7 0.7 0.6 0.4
39.0°C to ≤40.0°C 0.5 0.2 0.1 0.1 0.3 0.5
>40.0°C 0.0 0.0 0.0 0.0 0.0 0.1
Vomitingd
Anye3.7 1.9 2.2 1.4 1.7 2.2
Mild 2.8 1.7 1.7 1.1 1.4 1.7
Moderate 0.9 0.2 0.4 0.4 0.3 0.5
Severe 0.0 0.0 0.0 0.0 0.0 0.0
Diarrheaf
Anye10.6 12.1 7.6 9.1 7.7 7.6
Mild 9.1 10.9 6.2 7.6 6.4 6.2
Moderate 1.3 1.1 1.3 1.2 1.0 1.1
Severe 0.3 0.1 0.1 0.4 0.3 0.2
Headacheg
Anye51.8 37.2 37.8 28.1 35.4 24.8
Mild 28.7 24.0 20.2 15.7 18.9 13.5
Moderate 21.0 12.5 16.0 10.9 15.2 10.4
Severe 2.2 0.7 1.7 1.5 1.3 1.0
Fatigueg
Anye54.0 40.3 38.3 26.3 35.9 24.4
Mild 27.8 23.5 20.6 13.2 18.4 13.5
Moderate 23.2 15.2 15.8 11.7 15.2 10.0
Severe 3.0 1.7 1.9 1.4 2.3 0.9
Chillsg
Anye25.3 17.2 16.0 10.3 13.1 8.3
Mild 16.2 13.3 10.6 8.1 8.7 6.5
Moderate 8.0 3.5 4.8 1.8 3.8 1.7
Severe 1.2 0.4 0.6 0.5 0.5 0.1
Muscle pain (other than muscle pain at the injection site)g
Anye24.4 19.2 17.8 10.3 17.6 11.1
Mild 13.2 13.5 8.7 5.2 9.5 6.6
Moderate 10.1 5.4 7.9 4.5 7.2 4.3
Severe 1.2 0.3 1.2 0.6 0.8 0.2
Joint paing
Anye21.9 13.6 16.7 9.1 16.0 8.9
Mild 11.8 8.3 8.4 5.0 8.9 5.5
Moderate 8.7 4.6 7.5 3.4 5.9 3.0
Severe 1.4 0.7 0.8 0.7 1.2 0.4
Use of antipyretic
medication20.7 10.4 13.6 8.9 12.7 6.8
aStudy 1: National Clinical Trial (NCT) number NCT01830855.
bTrumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months.
cStudy 1: Fever (≥38°C): N=2679, 2540, and 2414 for Trumenba at Dose 1, Dose 2, and Dose 3, respectively; N=890, 840, and 819 for
FDA-CBER-2021-5683-0951385
7Table 3: Percentages of Subjects 10 to 18 Years of Age (Study 1a) Reporting Systemic Advers e Reactions and Use
of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabHAV/SalinebTrumenbabHAV/SalinebTrumenbabHAV/Salineb
Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
HAV/saline at Dose 1, Dose 2, and Dose 3, respectively.
dMild (1 -2 times in 24 hours); moderate (>2 times in 24 hours); severe (r equires intravenous hydration).
e"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of
vaccination.
fMild (2 -3 loose stools in 24 hours); moderate (4 -5 loose stools in 24 hour s); severe (6 or more loose stools in 24 hours).
gMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Table 4: Percentages of Subjects 18 to 25 Years of Age (Study 2a) Reporting Systemic Advers e Reactions and Use
of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabSalinebTrumenbabSalinebTrumenbabSalineb
Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
Fever ( ≥38°C)c
≥38.0°C 2.4 0.6 1.2 1.0 2.0 0.6
38.0°C to <38.5°C 1.6 0.4 0.7 0.6 1.4 0.5
38.5°C to <39.0°C 0.7 0.0 0.4 0.3 0.4 0.2
39.0°C to ≤40.0°C 0.0 0.3 0.1 0.1 0.1 0.0
>40.0°C 0.0 0.0 0.0 0.0 0.1 0.0
Vomitingd
Anye2.6 2.1 2.1 1.6 2.0 1.4
Mild 2.2 2.1 1.6 1.3 1.8 1.1
Moderate 0.4 0.0 0.5 0.3 0.2 0.3
Severe 0.0 0.0 0.0 0.0 0.0 0.0
Diarrheaf
Anye12.7 11.8 8.6 8.1 7.5 6.9
Mild 10.2 9.8 6.4 4.7 6.1 5.3
Moderate 2.4 1.9 1.7 2.8 1.2 1.3
Severe 0.2 0.1 0.5 0.6 0.2 0.3
Headacheg
Anye43.9 36.2 33.1 24.9 32.5 21.6
Mild 24.3 22.1 18.4 13.6 17.6 12.5
Moderate 17.9 13.5 13.3 10.1 13.3 8.3
Severe 1.6 0.6 1.4 1.3 1.6 0.8
Fatigueg
Anye50.9 39.8 39.2 27.3 39.3 24.5
Mild 25.4 23.2 20.6 13.9 18.9 13.1
Moderate 22.1 15.8 16.4 11.5 18.8 9.6
Severe 3.4 0.9 2.2 2.0 1.6 1.8
Chillsg
Anye18.1 9.8 12.4 8.5 12.6 6.4
Mild 12.0 8.1 8.1 6.9 7.7 4.3
Moderate 4.9 1.6 3.5 1.6 4.2 2.1
Severe 1.1 0.0 0.8 0.0 0.8 0.0
Muscle pain (other than muscle pain at the injection site)g
Anye25.9 14.5 15.6 8.5 16.9 7.5
Mild 13.0 9.6 7.6 5.8 8.9 4.5
Moderate 11.3 4.4 7.1 2.3 6.8 2.9
Severe 1.6 0.5 0.8 0.4 1.2 0.2
Joint paing
FDA-CBER-2021-5683-0951386
8Table 4: Percentages of Subjects 18 to 25 Years of Age (Study 2a) Reporting Systemic Advers e Reactions and Use
of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
TrumenbabSalinebTrumenbabSalinebTrumenbabSalineb
Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
Anye19.6 10.9 15.1 6.5 12.6 5.3
Mild 10.3 6.9 8.1 3.7 6.6 2.9
Moderate 7.9 3.5 6.2 2.5 5.4 2.4
Severe 1.4 0.5 0.9 0.3 0.6 0.0
Use of antipyretic
medication13.4 8.9 12.3 7.6 12.8 6.6
aStudy 2: National Clinical Trial (NCT) number NCT01352845.
bTrumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
cStudy 2: Fever ( ≥38°C): N=2415, 2067, and 1814 for Trumenba at Dose 1, Dose 2, a nd Dose 3, respectively; N=796, 705, and 621 for saline at
Dose 1, Dose 2, and Dose 3, respectively.
dMild (1 -2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
e"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of
vaccination.
fMild (2 -3 loose stools in 24 hours); moderate (4 -5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
gMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
The frequencies of adverse reactions were highest after the first dose regardless of the schedule. After
subsequent doses, t he frequencies of adverse reactions were similar regardless of dose number and schedule .
Serious Adverse Events
Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received at least one dose of
Trumenba, serious adverse events (SAEs) were reported by269 (1.8 %) subjects.
Among the 8 controlled studies (Trumenba N= 13,275 , control N= 5,501 ), SAEs were reported by 213(1.6%)
subjects and by 106 (1.9%) subjects who received at least one dose of Trumenba or control , respectively .
Non-serious Adverse Events
Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received Trumenba, non- serious
AEs within 30 day s after any dose were reported in 4,463 (29.3%) subjects. Among the 8 controlled studies
(Trumenba N=13,275, control N=5 ,501), AEs that occurred wit hin 30 day s of vaccination were reported in
4,056 (30.6%) subjects who received Trumenba and 1, 539 (28.0%) subjects in the control group, for individuals
who received at least one dose. AEs that occurred at a frequency of at least 2% and were more frequent ly
observed in subjects who received Trumenba than subjects in the control group were injection site pain, fever ,
and headache.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post- approval use of Trumenba . Because these
reactions are reported voluntarily from a population of uncertain size, it is not alway s possible to reliably
estimate their frequency or establish a causal relationship to product exposure .
Immune S ystem Disorders: Hy persensitivity reactions, incl uding anaph ylactic reactions.
Nervous s ystem disorder: Sy ncope (fainting).
7 DRUG INTERACTIONS
FDA-CBER-2021-5683-0951387
9In clinical trials, Trumenba was administered concomitantly with HPV4 in adolescents 11 to <18 years of age
and with MCV4 and Tdap in adolescents 10 to <13 y ears of age [see Clinical Studies (14.0 ) and Adverse
Reactions (6. 0)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
All pregnancies have a risk of birth defect, loss, o rother adverse outcomes. In the U.S. general population, the
estimated ba ckground risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to
4% and 15% to 20%, respectivel y. There are no adequate and well -controlled studies of Trumenba in pregnant
women. Available human data on Trumenba administer ed to pregnant women are insufficient to inform
vaccine -assoc iated risks in pregnancy .
Two developmental toxicity studies were performed in female rabbits administered T rumenba prior to mating
and during gestation. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL ). These studies
revealed no evidence of harm to the fetus or offspring (until weaning) due to T rumenba [see Animal Data].
Animal Data
Two developmental toxicity studies were performed in female rabbits. Animals were administer ed Trumenba by
intramuscular injection 17 day s and 4 day s prior to mating and on gestation Day s 10 and 24. The dose was
0.5mL at each occasion (a single human dose is 0.5 mL ).No adverse effects on pre -weaning development up to
post-natal day 21 were obse rved. There w ere no fetal malformations or variations observed due to the vaccine.
8.2 Lactation
Risk Summary
Availa ble data are not sufficient to assess the effects of Trumenba on the breastfed infant or on milk
production/excretion. The developmental and health benefits of breastfeeding should be considered along with
the mother’s clinical need for Trumenba and an y potential adverse effects on the breastfed child from Trumenba
or from the underly ing maternal condition. For preventive vaccines, the und erlying maternal condition is
susceptibility to disease prevented by the vaccine.
8.4 Pediatric Use
Safety and effectiveness have not been established in children <10 y ears of age. In a clinical study , 90% of
infants < 12 months of age who were vaccinated with a reduced dosage formulation had fever.
8.5 Geriatric Use
Safety and eff ectiveness of Trumenba in adults older than 65years of age have not been established.
11 DESCRIPTION
Trumenba is a sterile suspension composed of two recombinant lipidated f actor H binding protein (fHBP)
variants from N. meningitidis serogroup B, one from fHBP subfamil y A and one from subfamil y B(A05 and
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10B01, respectivel y).1The proteins are individuall y produced in E. coli . Production strains are grown in defined
fermentati on growth media to a specific density . The recombinant proteins are extracted from the production
strains and purified through a series of column chromatograph y steps. Polysorbate 80 (PS80) is added to the
drug substances and is present in the final drug p roduct.
Each 0.5 mL dose contain s 60 micrograms of each fHBP variant (total of 120 micrograms of protein) , 0.018 mg
of PS80 and 0.25 mg of Al³+as AlPO 4in 10 mM histidine buffered s aline at pH 6.0.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Protection against invasive meningococcal disease is conferred mainl y by complement -mediated antibody -
dependent killing of N. meningitidis . The effectiveness of Trumenba was assessed b y measuring serum
bactericidal activity using human complement (hSBA).
fHBP is one of man y proteins found on the surface of meningococci and contributes to the ability of the
bacterium to avoid host defenses. fHBPs can be categorized into two immunologicall y distinct subfamilies, A
and B.1The susceptibility of serogroup B menin gococci to complement- mediated antibody -dependent killing
following vaccination with Trumenba is dependent on both the antigenic similarity of the bacterial and vaccine
fHBP s, as well as the amount of fHBP expressed on the surface of the invading meningoco cci.
13 NONCLINICAL TOXICOLOGY
Trumenba has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility in males.
Vaccination of female rabbits with Trumenba had no effect on fertility [see Pregnancy (8.1)].
14 CLINICAL STUDIES
The immunogenicit y of Trumenba following the three -dose schedule (0, 2, and 6 month s) was evaluated in
individuals 10 to 25 y ears of age in the U .S., Canada ,and Europe (Studies 1 and 2) and following the two -dose
(0and 6 month s) andthree -dose schedules (0, 1-2, and 6 month s) in individuals 11 to 18 years of age in Europe
(Study 3). Serum bactericidal antibodies were measured with hSBA assay s that used each of four
meningococcal serogroup B strains. The sefour primary test strains express fHBP variants rep resenting the two
subfamilies (A and B) and, when taken together, are representative of meningococcal serogroup B strains
causing invasive disease in the U. S.and Europe. The studies assessed the proportions of subjects with a 4- fold
or greater increase in hSBA titer for each of the four primary strains . The studies also assessed the composite
response to the four primary strains combined (proportion of subjects who achieved a hSBA titer greater than or
equal to 1:8 ( three strains) or 1:16 ( onestrain ).To assess the effectiveness of the three -dose schedule of
Trumenba against diverse meningococcal serogroup B strains, the proportion of subjects achieving a defined
hSBA titer post-dose 3 was evaluated against a panel of 10 additional strains, each expressing a different fHBP
variant .
14.1Immunogenicity
The hSBA responses to each of the primary strains observed in U.S.subjects after the third dose of Trumenba
are presented for Study 1 and Study 2 in Table 5.
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11Table 5 :Percentages of U.S. Individuals 10 to 25 Years of Age With ≥4-fold rise in hSBA Titer and Composite
Response Following Administration of Trumenba on a 0 -, 2-, and 6 -Month Schedule for Four Primary Strains
(Studies 1 and 2)a,b,c,d
Study 1 Study 2
(10 to 18 Years of Age) (18 to 25 Years of Age)
n %
(95% CI)en %
(95% CI)e
Subfamily/Subgroup
fHBP Variantf,g
≥4-Fold Increase
PMB80 (A22) Dose 358786.2
(83.1, 88.9)64481.1
(77.8, 84.0)
PMB2001 (A56) Dose 352692.0
(89.4, 94.2)62190.7
(88.1, 92.8)
PMB2948 (B24) Dose 358581.9
(78.5, 84.9)63483.9
(80.8, 86.7)
PMB2707 (B44) Dose 355588.3
(85.3, 90.8)64379.3
(76.0, 82.4)
Composite hSBA responseh
Before Dose 15070.6
(0.1, 1.7)6103.3
(2.0, 5.0)
Dose 353785.7
(82.4, 88.5)62582.4
(79.2, 85.3)
Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human complement; LLOQ=lower
limit of quantitation; LOD=limit of detection.
Note: LLOQ = 1:16 for A22; 1:8 for A56, B24, and B44.
Note: The 4 -fold increase is defined as follows: (1) For subjects with a baseline hSBA titer <1:4, a response is defined as an hSBA titer ≥1:16. (2)
For subjects with a baseline hSBA titer ≥1:4, a response is defined as an hSBA titer ≥4 times the LLOQ or ≥4 times the baseline titer, whichever was
higher.
Note: Pre -specified criteria for assessment of hSBA responses (4 -fold rise in titer to each primary test strain, and titer above LLOQ for all four
primary test strains) among U.S. subje cts were met in these studies.
aEvalua ble immunogenicity population.
bStudy 1 = NCT01830855 and Study 2 = NCT01352845.
cStudy 1 : Group 1 (0, 2, and 6 months).
dStudy 2 : Group 1 (0, 2, and 6 months).
eExact 2 -sided confidence interval (Clopper -Pearson method) based up on the o bserved proportion of subjects.
fThe strains expressing variants A22, A56, B24, and B44 correspond to strains PMB80, PMB2001, PMB2948, and PMB2707, respective ly.
gFor the third dose, serum was obtained approximate ly 1 month after vaccination.
hComposite response = hSBA ≥ LLOQ for all 4 primary meningococcal B strains.
The hSBA responses against a panel of 10 additional strains observed in U.S.subjects after the third dose of
Trumenba are presented fo r Study 1 and Study 2 in Table 6.
Table 6. Percentages of U.S. Individuals 10 to 25 Years of Age With a hSBA Titer ≥ LLOQ Against 10 Additional
Strains Following Administration of Trumenba on a 0-, 2- , and 6 -Month Schedule (Study 1 and Study 2) -a,b
Study 1 Study 2
(10 to 18 Years of Age) (18 to 25 Years of Age)
n %
(95% CI)cn %
(95% CI)c
Subfamily/Subgroup
fHBP Variantd,e
A/N1C1
PMB3175 (A29) Before Dose 116911.2
(6.9, 17.0)16023.8
(17.4, 31.1)
Dose 317698.9
(96.0, 99.9)16298.8
(95.6, 99.9)
A/N1C 2 Before Dose 1 178 7.9 166 10.8
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12Table 6. Percentages of U.S. Individuals 10 to 25 Years of Age With a hSBA Titer ≥ LLOQ Against 10 Additional
Strains Following Administration of Trumenba on a 0-, 2- , and 6 -Month Schedule (Study 1 and Study 2) -a,b
Study 1 Study 2
(10 to 18 Years of Age) (18 to 25 Years of Age)
n %
(95% CI)cn %
(95% CI)c
PMB3010 (A06) (4.4, 12.8) (6.6, 16.6)
Dose 317997.8
(94.4, 99.4)16489.0
(83.2, 93.4)
A/N2C1
PMB3040 (A07) Before Dose 117037.6
(30.3, 45.4)16555.8
(47.8, 63.5)
Dose 317896.1
(92.1, 98.4)16595.2
(90.7, 97.9)
PMB824 (A12) Before Dose 11805.0
(2.3, 9.3)1664.8
(2.1, 9.3)
Dose 318076.1
(69.2, 82.1)16566.7
(58.9, 73.8)
PMB1672 (A15) Before Dose 117015.9
(10.7, 22.3)15930.2
(23.2, 38.0)
Dose 316686.7
(80.6, 91.5)15989.9
(84.2, 94.1)
A/N2C2
PMB1989 (A19) Before Dose 11745.7
(2.8, 10.3)15823.4
(17.1, 30.8)
Dose 317391.9
(86.8, 95.5)16394.5
(89.8, 97.4)
B/N6
PMB1256 (B03) Before Dose 11832.2
(0.6, 5.5)1645.5
(2.5, 10.2)
Dose 318192.3
(87.4, 95.7)16184.5
(77.9, 89.7)
PMB866 (B09) Before Dose 118012.2
(7.8, 17.9)16513.9
(9.0, 20.2)
Dose 318285.7
(79.8, 90.5)16272.2
(64.7, 79.0)
PMB431 (B15) Before Dose 118027.8
(21.4, 34.9)16333.1
(26.0, 40.9)
Dose 318397.3
(93.7, 99.1)16395.7
(91.4, 98.3)
PMB648 (B16) Before Dose 11806.7
(3.5, 11.4)16111.8
(7.3, 17.8)
Dose 318083.9
(77.7, 88.9)15972.3
(64.7, 79.1)
Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human complement; LLOQ=lower
limit of quantitation.
Note: LLOQ = 1:16 for A06, A12, and A19; 1:8 for A07, A15, A29, B03, B09, B15, and B16.
aThe e valuable immunogenicity population was used for the analysis.
bStudy 1 = NCT01830855 and Study 2 = NCT01352845.
cExact 2 -sided confidence interval (Clopper and Pearson) based upon the observed proportion of subjects.
dThe strains expressing variants A06 , A12, A19, A07, A15, A29, B03, B09, B15, and B16 correspond to strains PMB3010, PMB824, PMB1989,
PMB3040, PMB1672, PMB3175, PMB1256, PMB866, PMB431, and PMB648, respectively.
eFor the third dose, serum was obtained approximately 1 month after vaccination .
In Stud y 3, Trumenba was administered according to different schedules, including Group 1 (0, 1 ,and
6months) ,Group 2 (0, 2 ,and 6 months) and Group 3 (0 and 6 months). The hSBA responses observed after the
second dose in Groups 1, 2, and 3 and compl etion of the three -dose series in Group 1 and 2 are presented in
Table 7.
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13Table 7: Percentages of European Individuals 11 to 18 Years of Age With a ≥4-Fold Increase in hSBA Titer and
Composite Responsea,b
Group 1 Group 2 Group 3
3-Dose Schedule
(0, 1, and 6 Months)c3-Dose Schedule
(0, 2, and 6 Months)d2-Dose Schedule
(0 and 6 Months)e
fHBP Variantf,g%
(95% CI)h%
(95% CI)h%
(95% CI)h
≥4-Fold Increase
PMB80 (A22)
Dose 258.8
(51.4, 66.0)72.5
(66.4, 78.0)82.3
(76.3, 87.3)
Dose 377.6
(70.9, 83.4)87.7
(81.6, 92.3)NA
PMB2001 (A56)
Dose 287.8
(82.2, 92.2)90.7
(86.2, 94.1)90.1
(85.1, 93.8)
Dose 391.2
(86.1, 94.9)93.8
(88.8, 97.0)NA
PMB2948 (B24)
Dose 251.1
(43.6, 58.5)54.2
(47.7, 60.7)64.5
(57.4, 71.1)
Dose 374.1
(67.1, 80.2)78.3
(71.1, 84.4)NA
PMB2707 (B44)
Dose 248.1
(40.7, 55.6)53.4
(46.8, 59.9)66.0
(58.9, 72.6)
Dose 380.9
(74.5, 86.2)78.6
(71.4, 84.7)NA
Composite Responseg,i
Before Dose 14.6
(2.0, 8.8)2.2
(0.7, 5.0)1.5
(0.3, 4.4)
Dose 252.0
(44.3, 59.7)52.0
(45.3, 58.6)72.9
(65.9, 79.1)
Dose 380.3
(73.7, 85.9)81.8
(74.9, 87.4)NA
Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human co mplement; LLOQ=lower
limit of quantitation; NA=not applicable.
Note: LLOQ = 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).
Note: The ≥4-fold increase is defined as follows: (1) For subjects with a baseline hSBA titer <1:4 , a ≥4-fold increase was defined as an hSBA titer
≥1:16. (2) For subjects with a baseline hSBA titer ≥1:4, a ≥4 -fold increase was defined as an hSBA titer ≥4 times the LLOQ or ≥4 times the baseline
titer, whichever was higher.
aPer-schedule Evaluable populations. Dose 2 data include subjects who received two doses, irrespective of whether they received th e third dose.
bStudy 3: NCT01299480.
cGroup 1 (0, 1, a nd 6 months). The denominators ranged from 173 to 187 after Dose 2 and 178 to 188 after Dose 3, depending on the strain.
dGroup 2 (0, 2, and 6 months). The denominators ranged from 229 to 240 after Dose 2 and 159 to 162 after Dose 3, depending on the stra in.
eGroup 3 (0 and 6 months). The denominators ranged from 188 to 203 after Do se 2, depending on the strain.
fThe strains expressing variant A22, A56, B24, and B44 correspond to strains PMB80, PMB2001, PMB2948, and PMB2707, respectivel y.
gFor the second and third doses, serum was obtained approximately 1 month after vaccination.
hExact 2 -sided confidence interval (Clopper and Pearson) based upon the observed proportion of subjects.
iComposite response = hSBA ≥LLOQ for all 4 primary meningococcal B st rains.
14.2Concomitant Vaccine Administration
Study 4evaluated the immunogenicit y of concomitantly administered Trumenba and Human Papillomavirus
Quadrivalent (T ypes 6, 11, 16, and 18) Vaccine, Recombinant (HPV4) (Merck & Co, Inc.). U .S.subjects 11 to
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14<18years of age were randomized into three groups: Group 1 received Trumenba and HPV4 (N=992), Group 2
received Trumenba and saline (N=990), and Group 3 received saline and HPV4 (N=501). All vaccines were
administered according to a 0, 2 and 6 month sch edule. Immune responses were evaluated b y comparisons of
geometric mean titer [GMT] for each HPV t ype at 1 month after the third HPV4 vaccination (Group 1 vs.
Group 3), and hSBA GMTs using two meningococcal serogroup B strains [variants A22 and B24] 1 mont h after
thethird Trumenba vaccination (Group 1 vs .Group 2).The noninferiority criteria for the comparisons of GMTs
[lower limit of the 2- sided 95% confidence interval (CI) of the GMT ratio (Group 1/Group 3 for HPV and
Group 1/Group 2 for meningococcal serogroup B strains) >0.67 ]were met for three HPV ty pes (6, 11 and 16)
and for the meningococcal serogroup B stra instested . For HPV- 18, the lower bound of the 95% CI for the GMT
ratio was 0.62 at one month after the third HPV4 vaccination .
Study 5evalua ted the immunogenicit y of concomitantly administered Trumenba and Meningococcal
Polysaccharide (Serogroups A, C, Y and W -135) Diphtheria Toxoid Conjugate Vaccine (MCV4) (Sanofi
Pasteur Inc.) and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertu ssis Vaccine Adsorbed
(Tdap) (Sanofi Pasteur Ltd.) vaccines. U .S.subjects 10to <13 y ears of age were randomized into three groups:
Group 1 received Trumenba at 0, 2, and 6 months , and MCV4 and Tdap were coadministered with the first
Trumenba dose (N=883) . Group 2 received saline at 0, 2 and 6 months, and MCV4 and Tdap were
coadministered with the first saline injection (N=870). Group 3 received Trumenba at 0, 2 and 6 months, and
saline was coadministered with the first Trumenba dose (N=875). Immune responses were evaluated by
comparisons of GMTs for each of the MCV4 and Tdap antigens 1 month after the first Trumenba vaccination ,
and hSBA GMTs using two meningococcal serogroup B strains [variants A22 and B24] 1 month after the third
Trumenba vaccination . The noninferiorit y criteri afor the comparisons of GMT s [lower limit of the 2 -sided 95%
CI of the GMT ratio (Group 1/Group 3 for meningococcal sero group B strains and Group 1/Group 2for MCV4
and Tdap) >0.67] w eremet for all antigens.
15 REFERENCES
1.Wang X , et al. Prevalence and genetic diversit y of candidate vaccine antigens among invasive Neisseria
meningitidis isolates in the U .S. Vaccine 2011; 29:4739-4744.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Trumenba is supplied in the following s trengths and package configurations:
Prefilled Sy ringe, 1 Dose (10 per package) – NDC 0005-0100-10.
Prefilled Sy ringe, 1 Dose (5 per package) – NDC 0005-0100-05.
Prefilled Sy ringe, 1 Dose (1 per package) – NDC 0005-0100- 02 (This Package Not for Sale).
After shipping, Trumenba may arrive at temperatures between 2 °C to 25°C ( 36°F to 77°F).
The tip cap and rubber plunger of the prefilled s yringe are not made with natural rubber latex.
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1516.2 Storage and Handling
Upon receipt, store refrigerated at 2°C to 8 °C (36°F to 46°F).
Store s yringes in the refrigerator horizontally (laying flat on the shelf) to minimize the re -dispersion time .
Do not freeze. Discard if the vaccine has been frozen.
17 PATIENT COUNSELING INFORMATION
Prior to administration of this vaccine, the healthcare professional should inform the individual, parent,
guardian, or other responsible adult of the following:
The importance of completing the immunization series.
Report a ny suspected adverse reactions to ahealthcare professional.
Provide the Vaccine Information Statements , which are available free of charge at the Centers for Disease
Control and Prevention (CDC) website ( www.cdc.gov/vaccines ).
U.S.Govt. L icense No. 3
LAB -0722-9 .0
CPT Code 90621
FDA-CBER-2021-5683-0951394