INDICATIONS
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.
APPROVAL OF TRUMENBA IS BASED ON DEMONSTRATION OF IMMUNE RESPONSE, AS MEASURED BY SERUM BACTERICIDAL ACTIVITY AGAINST FOUR SEROGROUP B STRAINS REPRESENTATIVE OF PREVALENT STRAINS IN THE UNITED STATES. THE EFFECTIVENESS OF TRUMENBA AGAINST DIVERSE SEROGROUP B STRAINS HAS NOT BEEN CONFIRMED.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
TRUMENBA IS A SUSPENSION FOR INTRAMUSCULAR INJECTION IN 0.5 ML SINGLE-DOSE PREFILLED SYRINGE.
TRUMENBA IS SUPPLIED IN THE FOLLOWING STRENGTHS AND PACKAGE CONFIGURATIONS:
PREFILLED SYRINGE, 1 DOSE (10 PER PACKAGE) - NDC 0005-0100-10.
PREFILLED SYRINGE, 1 DOSE (5 PER PACKAGE) - NDC 0005-0100-05.
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 SYRINGE ARE NOT MADE WITH NATURAL RUBBER LATEX.
STORAGE AND HANDLING
UPON RECEIPT, STORE REFRIGERATED AT 2°C TO 8°C (36°F TO 46°F).
STORE SYRINGES 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.
MANUFACTURED BY: WYETH PHARMACEUTICALS INC., A SUBSIDIARY OF PFIZER INC., PHILADELPHIA, PA 19101. REVISED: OCTOBER 2014
DOSAGE AND ADMINISTRATION
FOR INTRAMUSCULAR USE ONLY.
DOSE AND SCHEDULE
ADMINISTER TRUMENBA AS A THREE DOSE SERIES (0.5 ML EACH) ACCORDING TO A 0-, 2-, AND 6-MONTH SCHEDULE.
ADMINISTRATION
SHAKE SYRINGE VIGOROUSLY 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 VISUALLY 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 INTRAMUSCULARLY, USING A STERILE NEEDLE ATTACHED TO THE SUPPLIED PREFILLED SYRINGE. THE PREFERRED SITE FOR INJECTION IS THE DELTOID MUSCLE OF THE UPPER ARM. DO NOT MIX TRUMENBA WITH ANY OTHER VACCINE IN THE SAME SYRINGE.
USE OF TRUMENBA WITH OTHER MENINGOCOCCAL GROUP B VACCINES
SUFFICIENT DATA ARE NOT AVAILABLE ON THE SAFETY AND EFFECTIVENESS OF USING TRUMENBA AND OTHER MENINGOCOCCAL GROUP B VACCINES INTERCHANGEABLY TO COMPLETE THE VACCINATION SERIES.
SIDE EFFECTS
IN CLINICAL STUDIES, THE MOST COMMON SOLICITED ADVERSE REACTIONS WERE PAIN AT THE INJECTION SITE ( ? 85%), FATIGUE ( ? 40%), HEADACHE ( ? 35%), MUSCLE PAIN ( ? 30%), AND CHILLS ( ? 15%).
CLINICAL TRIALS EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIALS OF A VACCINE CANNOT BE DIRECTLY COMPARED TO RATES IN THE CLINICAL TRIALS OF ANOTHER VACCINE AND MAY NOT REFLECT THE RATES OBSERVED IN CLINICAL PRACTICE.
THE SAFETY OF TRUMENBA WAS EVALUATED IN 4,282 SUBJECTS 11 THROUGH 25 YEARS OF AGE IN 7 CLINICAL STUDIES (4 RANDOMIZED CONTROLLED AND 3 SUPPORTIVE NON-CONTROLLED STUDIES) CONDUCTED IN THE US, EUROPE, AND AUSTRALIA. A TOTAL OF 4,250 ADOLESCENTS (11 THROUGH 18 YEARS OF AGE) AND 32 ADULTS (19 THROUGH 25 YEARS OF AGE) RECEIVED AT LEAST ONE DOSE OF TRUMENBA. A TOTAL OF 1,004 SUBJECTS 11 THROUGH 25 YEARS OF AGE IN THE CONTROL GROUPS RECEIVED SALINE PLACEBO AND/OR ONE OF THE FOLLOWING VACCINES: HUMAN PAPILLOMAVIRUS QUADRIVALENT (TYPES 6, 11, 16, AND 18) VACCINE, RECOMBINANT [HPV4]; A NON-US LICENSED TETANUS TOXOID, REDUCED DIPHTHERIA TOXOID, ACELLULAR PERTUSSIS AND INACTIVATED POLIO VIRUS VACCINE; OR TETANUS TOXOID, REDUCED DIPHTHERIA TOXOID AND ACELLULAR PERTUSSIS VACCINE ADSORBED (SANOFI PASTEUR LTD.).
THE SAFETY EVALUATION IN THE 7 STUDIES INCLUDED AN ASSESSMENT OF: (1) SOLICITED LOCAL AND SYSTEMIC REACTIONS, AND USE OF ANTIPYRETIC 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 MONTH OR 6 MONTHS AFTER THE LAST VACCINATION, DEPENDING ON THE STUDY 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 7 STUDIES, AMONG THE SUBJECTS WHO RECEIVED TRUMENBA, 56.1% WERE MALE AND 44.0% WERE FEMALE, AND THE MAJORITY WERE WHITE (90.8%) AND NON-HISPANIC/NON-LATINO (91.4%).
SOLICITED LOCAL AND SYSTEMIC ADVERSE REACTIONS
IN A RANDOMIZED, ACTIVE-CONTROLLED, OBSERVER-BLINDED, MULTICENTER TRIAL IN THE US, 1,982 ADOLESCENTS 11 TO < 18 YEARS OF AGE RECEIVED TRUMENBA AT 0-, 2-, AND 6-MONTHS. SUBJECTS WERE RANDOMIZED TO 1 OF 3 GROUPS: TRUMENBA + HPV4 (GROUP 1), TRUMENBA + SALINE (GROUP 2), SALINE + HPV4 (GROUP 3). 81.6% OF SUBJECTS WERE WHITE, 13% WERE BLACK OR AFRICAN-AMERICAN, 1.2% WERE ASIAN AND 17.4% WERE HISPANIC OR LATINO. OVERALL, 66.5% OF SUBJECTS WERE MALE, 65.9% OF PARTICIPANTS WERE 11 TO ? 14 YEARS AGE AND 34.1% WERE 15 TO < 18 YEARS OF AGE.
LOCAL ADVERSE REACTIONS AT THE TRUMENBA INJECTION SITE (GROUPS 1 AND 2), AND SALINE INJECTION SITE (GROUP 3) WERE ASSESSED IN THIS STUDY. TABLE 1 PRESENTS THE PERCENTAGE AND SEVERITY OF REPORTED LOCAL ADVERSE REACTIONS WITHIN 7 DAYS FOLLOWING EACH DOSE OF TRUMENBA (GROUPS 1 AND 2 COMBINED) OR SALINE CONTROL (GROUP 3).
LOCAL ADVERSE REACTIONS WERE REPORTED MORE FREQUENTLY FOLLOWING TRUMENBA COMPARED TO SALINE (SEE TABLE 1).
TABLE 1: PERCENTAGE OF SUBJECTS 11 TO < 18 YEARS OF AGE REPORTING LOCAL ADVERSE REACTIONS WITHIN 7 DAYS AFTER EACH VACCINATIONA
LOCAL REACTION TRUMENBA SALINE
DOSE 1
N=1970 DOSE 2
N=1826 DOSE 3
N=1688 DOSE 1
N=496 DOSE 2
N=468 DOSE 3
N=438
PAINB
ANYC 92.8 86.1 84.5 36.9 29.1 23.3
MILD 42.5 49.9 44.1 33.1 24.6 20.8
MODERATE 42.1 31.6 34.7 3.6 4.5 2.3
SEVERE 8.2 4.6 5.7 0.2 0.0 0.2
REDNESSD
ANYC 20.4 14.9 15.8 1.2 1.7 1.1
MILD 9.0 6.6 7.3 1.0 1.7 0.9
MODERATE 9.1 7.0 7.0 0.2 0.0 0.2
SEVERE 2.2 1.3 1.4 0.0 0.0 0.0
SWELLINGD
ANYC 21.6 18.2 20.1 2.8 2.8 1.8
MILD 12.5 10.8 11.7 1.8 2.1 1.4
MODERATE 8.5 7.1 8.2 1.0 0.6 0.5
SEVERE 0.5 0.3 0.2 0.0 0.0 0.0
A NATIONAL CLINICAL TRIAL (NCT) NUMBER NCT01461993
B MILD (DOES NOT INTERFERE WITH ACTIVITY); MODERATE (INTERFERES WITH ACTIVITY); SEVERE (PREVENTS DAILY ACTIVITY).
C "ANY" IS DEFINED AS THE CUMULATIVE FREQUENCY OF SUBJECTS WHO REPORTED A REACTION AS "MILD", "MODERATE" OR "SEVERE" WITHIN 7 DAYS OF VACCINATION.
D MILD (2.5-5.0 CM); MODERATE (5.5-10.0 CM); SEVERE ( > 10.0 CM).
TABLE 2 PRESENTS THE PERCENTAGE OF SUBJECTS WHO HAD AT LEAST ONE INJECTION AND WHO ALSO REPORTED A SOLICITED SYSTEMIC ADVERSE REACTION WITHIN 7 DAYS OF VACCINATION, BY STUDY GROUP. THESE REACTIONS RESOLVED WITHIN 8 DAYS IN 90% OF SUBJECTS. FEVER (TEMPERATURE ? 38.0°C) RESOLVED WITHIN 3 DAYS IN 84% OF SUBJECTS.
TABLE 2: PERCENTAGE OF SUBJECTS 11 TO < 18 YEARS OF AGE REPORTING SYSTEMIC ADVERSE REACTIONS AND USE OF ANTIPYRETIC MEDICATIONS WITHIN 7 DAYS AFTER EACH VACCINATIONA
SERIOUS ADVERSE EVENTS
OVERALL IN CLINICAL STUDIES IN WHICH 4282 SUBJECTS 11 THROUGH 25 YEARS OF AGE RECEIVED AT LEAST ONE DOSE OF TRUMENBA, SERIOUS ADVERSE EVENTS WERE REPORTED IN 88 (2.0%) SUBJECTS. AMONG THE 4 CONTROLLED STUDIES (TRUMENBA N=2557, CONTROL N=1004), SERIOUS ADVERSE EVENTS WERE REPORTED IN 44 (1.7%) SUBJECTS WHO RECEIVED TRUMENBA AND 16 (1.6%) CONTROL SUBJECTS, FOR INDIVIDUALS WHO RECEIVED AT LEAST ONE DOSE.
NON-SERIOUS ADVERSE EVENTS
OVERALL IN CLINICAL STUDIES IN WHICH 4282 SUBJECTS 11 THROUGH 25 YEARS OF AGE RECEIVED TRUMENBA, NON-SERIOUS AES WITHIN 30 DAYS AFTER ANY DOSE WERE REPORTED IN 1049 (24.5%) SUBJECTS. AMONG THE 4 CONTROLLED STUDIES (TRUMENBA N=2557, CONTROL N=1004), AES THAT OCCURRED WITHIN 30 DAYS OF VACCINATION WERE REPORTED IN 739 (28.9%) SUBJECTS WHO RECEIVED TRUMENBA AND 313 (31.2%) 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 FREQUENTLY OBSERVED IN SUBJECTS WHO RECEIVED TRUMENBA THAN SUBJECTS IN THE CONTROL GROUP WERE INJECTION SITE PAIN AND HEADACHE.
READ THE TRUMENBA (MENINGOCOCCAL GROUP B VACCINE) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
PROTECTION AGAINST INVASIVE MENINGOCOCCAL DISEASE IS CONFERRED MAINLY BY COMPLEMENT-MEDIATED ANTIBODY-DEPENDENT KILLING OF N. MENINGITIDIS. THE EFFECTIVENESS OF TRUMENBA WAS ASSESSED BY MEASURING SERUM BACTERICIDAL ACTIVITY USING HUMAN COMPLEMENT (HSBA).
FHBP IS ONE OF MANY 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 IMMUNOLOGICALLY DISTINCT SUBFAMILIES, A AND B.1 THE SUSCEPTIBILITY OF SEROGROUP B MENINGOCOCCI TO COMPLEMENT-MEDIATED ANTIBODY-DEPENDENT KILLING FOLLOWING VACCINATION WITH TRUMENBA IS DEPENDENT ON BOTH THE ANTIGENIC SIMILARITY OF THE BACTERIAL AND VACCINE FHBPS, AS WELL AS THE AMOUNT OF FHBP EXPRESSED ON THE SURFACE OF THE INVADING MENINGOCOCCI.
CLINICAL STUDIES
IN A RANDOMIZED STUDY CONDUCTED IN THE US, THE IMMUNOGENICITY OF TRUMENBA FOLLOWING A 3-DOSE SERIES WAS EVALUATED IN ADOLESCENTS (11 TO < 18 YEARS OF AGE). SERUM BACTERICIDAL ANTIBODIES WERE MEASURED WITH HSBA ASSAYS THAT USED EACH OF FOUR MENINGOCOCCAL GROUP B STRAINS. THE FOUR TEST STRAINS EXPRESS FHBP VARIANTS REPRESENTING THE TWO SUBFAMILIES (A AND B) AND, WHEN TAKEN TOGETHER, ARE REPRESENTATIVE OF PREVALENT STRAINS IN THE US. THE STUDIES ASSESSED THE PROPORTIONS OF SUBJECTS WITH A 4-FOLD OR GREATER INCREASE IN HSBA TITER FOR EACH OF THE FOUR STRAINS, AND THE PROPORTION OF SUBJECTS WHO ACHIEVED A TITER GREATER THAN OR EQUAL TO THE LOWER LIMIT OF QUANTITATION (LLOQ) OF THE ASSAY FOR ALL FOUR STRAINS (COMPOSITE RESPONSE). THE LLOQ WAS DEFINED AS THE LOWEST AMOUNT OF THE ANTIBODY IN A SAMPLE THAT CAN BE RELIABLY QUANTIFIED.
IMMUNOGENICITY
IN AN ACTIVE-CONTROLLED, OBSERVER-BLINDED, MULTICENTER TRIAL CONDUCTED IN THE US, ADOLESCENTS 11 TO < 18 YEARS OF AGE, WERE ASSIGNED RANDOMLY INTO 3 GROUPS: GROUP 1 RECEIVED TRUMENBA + HPV4, GROUP 2 RECEIVED TRUMENBA + SALINE, AND GROUP 3 RECEIVED SALINE + HPV4 [SEE CLINICAL TRIAL EXPERIENCE]. THE HSBA RESPONSES OBSERVED AFTER THE SECOND DOSE AND COMPLETION OF A 3-DOSE SERIES ARE PRESENTED IN TABLE 3.
TABLE 3: PERCENTAGE OF ADOLESCENTS WITH A ? 4-FOLD RISE IN HSBA TITER AND COMPOSITE RESPONSEA,B
FHBP VARIANTD GROUP 1C GROUP 2C
TRUMENBA + HPV4 TRUMENBA + SALINE
%(95% CI)E %(95% CI)E
4-FOLD RESPONSEF
A22
DOSE 2 73.1(69.9, 76.2) 74.2(71.0, 77.3)
DOSE 3 85.3(82.6, 87.7) 86.4(83.8, 88.7)
A56
DOSE 2 92.5(90.4, 94.3) 92.6(90.4, 94.4)
DOSE 3 95.0(93.2, 96.5) 95.3(93.6, 96.8)
B24
DOSE 2 61.3(57.7, 64.8) 63.4(59.9, 66.9)
DOSE 3 83.4(80.5, 85.9) 84.8(82.0, 87.2)
B44
DOSE 2 45.7(42.1, 49.3) 47.4(43.8, 51.0)
DOSE 3 77.0(73.9, 79.9) 80.7(77.8, 83.4)
COMPOSITE RESPONSEF,G
BEFORE DOSE 1 0.3 (0.0, 1.0) 0.7 (0.2, 1.6)
DOSE 2 49.9(46.1, 53.6) 51.9(48.2, 55.6)
DOSE 3 81.0(78.0, 83.7) 83.9(81.1, 86.4)
ABBREVIATIONS: CI = CONFIDENCE INTERVAL; HSBA = SERUM BACTERICIDAL ACTIVITY MEASURED USING HUMAN COMPLEMENT; LLOQ = LOWER LIMIT OF QUANTITATION. NOTE: LLOQ = 1:16 FOR PMB80 (A22); 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 RESPONSE WAS DEFINED AS AN HSBA TITER ? 1:16. (2) FOR SUBJECTS WITH A BASELINE HSBA TITER ? 1:4, A 4-FOLD RESPONSE WAS DEFINED AS AN HSBA TITER ? 4 TIMES THE LLOQ OR ? 4 TIMES THE BASELINE TITER, WHICHEVER WAS HIGHER.
A EVALUABLE IMMUNOGENICITY POPULATION.
B NCT01461993
C THE DENOMINATOR RANGED FROM 710-792 FOR GROUP 1; 723-788 FOR GROUP 2.
D THE STRAINS EXPRESSING VARIANT A22, A56, B24, AND B44 CORRESPOND TO STRAINS PMB80, PMB2001, PMB2948, AND PMB2707, RESPECTIVELY.
E EXACT 2-SIDED CONFIDENCE INTERVAL (CLOPPER AND PEARSON) BASED UPON THE OBSERVED PROPORTION OF SUBJECTS.
F SERUM WAS OBTAINED APPROXIMATELY ONE MONTH AFTER THE SECOND AND ONE MONTH AFTER THE THIRD DOSES. G COMPOSITE RESPONSE = HSBA ? LLOQ FOR ALL 4 PRIMARY MENINGOCOCCAL B STRAINS.
IN A STUDY CONDUCTED IN EUROPE IN WHICH SUBJECTS 11 THROUGH 18 YEARS OF AGE WERE ADMINISTERED TRUMENBA ON A 0-, 2-, 6-MONTH SCHEDULE, THE HSBA RESPONSES FOLLOWING COMPLETION OF THE 3-DOSE SERIES WERE SIMILAR TO THOSE SHOWN IN TABLE 3.
CONCOMITANT VACCINE ADMINISTRATION
IN A STUDY CONDUCTED IN THE US, THE IMMUNOGENICITY OF CONCOMITANTLY ADMINISTERED TRUMENBA AND HPV4 WAS EVALUATED IN ADOLESCENTS 11 TO < 18 YEARS OF AGE [SEE CLINICAL STUDIES AND ADVERSE REACTIONS]. IMMUNE RESPONSES WERE EVALUATED BY COMPARISONS OF GEOMETRIC MEAN TITER [GMT] FOR EACH HPV TYPE 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 MONTH AFTER THE THIRD TRUMENBA VACCINATION (GROUP 1 VS. GROUP 2).
THE NONINFERIORITY CRITERIA FOR COMPARISONS OF THE GMT RATIO (LOWER LIMIT OF THE 2-SIDED 95% CONFIDENCE INTERVAL OF THE GMT RATIO > 0.67) WERE MET FOR THREE HPV TYPES (6, 11 AND 16) AND FOR THE MENINGOCOCCAL SEROGROUP B STRAINS. FOR HPV-18, THE LOWER BOUND OF THE 95% CONFIDENCE INTERVAL (CI) FOR THE GMT RATIO WAS 0.62 AT ONE MONTH AFTER THE THIRD HPV4 VACCINATION.
REFERENCES
1. WANG X, ET AL. PREVALENCE AND GENETIC DIVERSITY OF CANDIDATE VACCINE ANTIGENS AMONG INVASIVE NEISSERIA MENINGITIDIS ISOLATES IN THE UNITED STATES. VACCINE 2011; 29:4739-4744.