Trumenba

The vaccine is a homogeneous white suspension.
1 dose (0.5 ml) contains: MnB rLP2086 subfamily A 60 µg, MnB rLP2086 subfamily B 60 µg.
Excipients/Inactive Ingredients: Sodium Chloride, Histidine, Water for Injection, Aluminium Phosphate (AlPO₄), Polysorbate 80.

Pharmacotherapeutic group: vaccines.
Pharmacology: Pharmacodynamics: Mechanism of action: Protection against invasive meningococcal disease is mediated by serum bactericidal antibodies to bacterial surface antigens. Bactericidal antibodies act in concert with human complement to kill meningococci. This process is measured in vitro with serum bactericidal assay using human complement (hSBA) for serogroup B. A positive response in SBA is an accepted correlate of protection from meningococcal disease.
Trumenba [bivalent rLP2086] is a vaccine composed of two recombinant lipidated factor H binding proteins (fHbps) and prevents serogroup B disease by inducing broadly protective bactericidal antibody responses against epidemiologically diverse serogroup B strains. fHbp is found on the surface of meningococcal bacteria and is essential for bacteria to avoid host immune defenses. fHbps segregate into two immunologically distinct subfamilies, A and B, and >95% of serogroup B strains express fHbps from either subfamily.
Vaccination with Trumenba, which contains one fHbp each from subfamily A and B, elicits bactericidal antibodies directed against fHbp found on the surface of N. meningitidis serogroup B strains.
Clinical efficacy: The efficacy of Trumenba has not been evaluated through clinical trials. Vaccine efficacy has been inferred by demonstrating the induction of serum bactericidal antibody responses to four meningococcal serogroup B test strains (see the Immunogenicity as follows). The four test strains express fHbp variants representing the two subfamilies (A and B) and, when taken together, are representative of prevalent strains causing invasive disease. The studies assessed the proportions of subjects with a response (hSBA titer of at least 1:8 or 1:16 depending on the hSBA strain), the proportions of subjects with a 4-fold or greater increase from baseline in hSBA titer for each of the four strains and the composite response (a response for the four hSBA strains combined). The studies also assessed the proportion of subjects achieving a defined hSBA titer against a panel of 10 additional strains, each expressing a different fHbp variant. These additional hSBAs support and extend the breadth of vaccine coverage demonstrated by the 4 representative primary strains.
Immunogenicity: The immunogenicity of Trumenba described in this section is based on results from four clinical studies: Following the two-dose schedule (0 and 6 months) in subjects 10 to 25 years of age in the United States (US) and Europe (Study B1971057 [Study 1057]); Following the three-dose schedule (0, 2, and 6 months) in subjects 10 to 25 years of age globally (Studies B1971009 [Study 1009] and B1971016 [Study 1016]); Following the two-dose (0 and 6 months) and three-dose schedules (0, 1-2, and 6 months) in subjects 11 to 18 years of age in Europe (Study B1971012 [Study 1012]).
Study 1057 is a Phase 3, randomized, active-controlled, observer-blinded, multicenter trial in which subjects received Trumenba at 0 and 6 months (Trumenba was coadministered with MenACWY-CRM for the first dose) or an investigational pentavalent meningococcal vaccine at 0 and 6 months. The hSBA responses to four test strains observed after the second dose of Trumenba are presented in Table 1. (See Table 1.)

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The proportion of subjects achieving a defined hSBA titer after 2 doses of Trumenba, administered on a 0- and 6-month schedule, was evaluated against a panel of 10 additional strains, each expressing a different fHbp variant (see Table 2).

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Study 1009 was a Phase 3, randomized, active-controlled, observer-blinded, multicenter trial in which subjects aged 10 to 18 years received 1 of 3 lots (Groups 1, 2, and 3) of Trumenba or the active control hepatitis A virus (HAV) vaccine/saline (Group 4). The study assessed the safety, tolerability, immunogenicity, and demonstration of manufacturability of 3 lots of Trumenba administered on a 0-, 2-, and 6-month schedule. The hSBA responses to four test strains observed after the third dose in Group 1 and 4 are presented in Table 3. Results from Groups 2 and 3 are not presented, as only 2 representative strains were evaluated. Similar results were observed in Groups 2 and 3 as observed in Group 1.
Study 1016 was a Phase 3, randomized, placebo-controlled, observer-blinded, multicenter trial in which subjects 18 to 25 years of age were assigned to 2 groups in a 3:1 ratio (Group 1: Group 2). Group 1 received Trumenba at months 0, 2, and 6. Group 2 received saline at months 0, 2, and 6. The hSBA responses to four test strains observed after the third dose in Group 1 and 2 are presented in Table 3. (See Table 3.)

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In Studies 1009 and 1016, the proportion of subjects achieving a defined hSBA titer after 3 doses of Trumenba, administered on a 0-, 2-, and 6-month schedule, was evaluated against a panel of 10 additional strains, each expressing a different fHbp variant (see Table 4).

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In Study 1012, Trumenba was administered according to the following schedules: Group 1 (0, 1, and 6 months); Group 2 (0, 2, and 6 months); Group 3 (0 and 6 months); Group 4 (0 and 2 months); Group 5 (0 and 4 months) [see Adverse Reactions]. The hSBA responses observed after the second or third dose for Groups 1, 2 and 3 are presented in Table 5. (See Table 5.)

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Limited immunogenicity data is available for subjects 40 years and above.
Concomitant vaccine administration: In Study B1971010 (Study 1010) conducted in Europe, the immunogenicity of dTaP-IPV (a combined low-dose diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis virus vaccine) given concomitantly with the first dose of Trumenba was evaluated in adolescents 11 to 18 years of age. Noninferiority was demonstrated, as the lower limit of the 2-sided 95% CI for the difference in proportion of responders between the Trumenba + dTaP-IPV group (Group 1) and the dTaP-IPV-alone group (Group 2) 1 month after the dTaP-IPV dose was greater than -0.10 (-10%) for the 9 antigens in dTaP-IPV (i.e., the lowest lower bound of the 95% CI on the proportion difference was -4.7% [pertussis toxoid]).
In Study B1971011 (Study 1011) conducted in the US, the immunogenicity of concomitantly administered Trumenba and HPV4 vaccine was evaluated in adolescents 11 to 17 years of age. Immune responses were evaluated by comparisons of geometric mean titers (GMTs) for each human papillomavirus (HPV) type at 1 month after the third HPV4 vaccination and hSBA GMTs using two meningococcal serogroup B test strains [variants A22 and B24] 1 month after the third vaccination with Trumenba. 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. One month after Dose 3 with HPV4, ≥99% of subjects seroconverted to all 4 HPV antigens in both the saline + HPV4 and Trumenba + HPV4 groups.
In Study B1971015 (Study 1015) conducted in the US, the immunogenicity of concomitantly administered Trumenba with meningococcal polysaccharide (serogroups A, C, Y and W 135) diphtheria toxoid conjugate (MenACWY) and Tdap vaccines was evaluated in adolescents 10 to 12 years of age. Immune responses were evaluated by comparisons of GMTs for each of 10 MenACWY and Tdap antigens 1 month after the first vaccination. The criterion for the noninferiority margin of 1.5-fold was met for all MenACWY and Tdap antigens.
Persistence of immunity and response to booster vaccination: Study B1971033 (Study 1033) was an open-label, follow-up study of subjects previously enrolled in a primary study, including Study 1012. Subjects attended visits over 4 years for collection of blood samples and received a single booster dose of Trumenba approximately 4 years after receipt of a primary series of 2 or 3 doses of Trumenba.
The hSBA responses 4 years after the primary series and 26 months after the booster dose for subjects enrolled from primary Study 1012 Group 1 (0, 1, and 6 months), Group 2 (0, 2, and 6 months), and Group 3 (0 and 6 months) are presented in Tables 6 and 7. (See Tables 6 and 7.)

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Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data revealed no special hazard for humans based on conventional studies of repeated dose toxicity, local tolerance, and reproduction and developmental toxicity.
Reproduction studies performed in female rabbits at doses equivalent to the highest administered human dose have revealed no evidence of impaired female fertility or harm to the fetus due to Trumenba. Because animal reproductive studies are not always predictive of the human response, this vaccine should be used during pregnancy only if clearly needed. Trumenba has not been evaluated for impairment of fertility in males.

Trumenba is indicated in individuals 10 years and older for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B.
See Pharmacology: Pharmacodynamics under Actions for information on protection against specific serogroup B strains.
Dosing of Trumenba should be determined taking into consideration the risk of invasive meningococcal B disease by each country or region. The use of this vaccine should be in accordance with official recommendations.

Posology: Standard schedule for routine immunization: Administer 0.5 ml at 0 and 6 months.
Schedule for individuals at increased risk of invasive meningococcal disease: Administer 2 doses of 0.5 ml at least 1 month apart, followed by a third dose at least 4 months after the second dose.
Booster Dose: A booster dose should be considered following either dosing regimen for individuals at continued risk of invasive meningococcal disease (see Pharmacology: Pharmacodynamics under Actions).
Pediatric Population: Safety and efficacy of Trumenba in children below the age of 10 years of age have not been established.
Elderly: Trumenba has not been studied in adults older than 65 years of age.
Method of administration: For intramuscular injection only. The preferred site for injection is the deltoid muscle of the upper arm.
Separate injection sites and different syringes must be used if more than one vaccine is administered at the same time.
There are no data available on the interchangeability of Trumenba with other meningococcal serogroup B vaccines to complete the vaccination series.

Experience of overdose is limited. Overdose with Trumenba is unlikely because it is provided in a prefilled syringe.
In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

Hypersensitivity to the active substances or to any of the excipients listed in Description.
Severe allergic reaction (e.g., anaphylaxis) after any previous dose of Trumenba or to any component of this vaccine.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. Do not inject intravenously, intradermally, or subcutaneously.
As with other injectable vaccines, syncope (fainting) can occur in association with administration of Trumenba. Procedures should be in place to avoid injury from fainting.
Vaccination should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result in the deferral of vaccination.
As with any intramuscular vaccine, Trumenba should be given with caution to individuals with thrombocytopenia or any coagulation disorder or to those receiving anticoagulant therapy, unless the potential benefit clearly outweighs the risk of administration.
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to Trumenba.
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 Neisseria meningitidis serogroup B even if they develop antibodies following vaccination with Trumenba.
As with any vaccine, vaccination with Trumenba may not protect all vaccine recipients.
Effects on ability to drive and use machines: Trumenba has no or negligible influence on the ability to drive and use machines.

Pregnancy: There are no data from the use of Trumenba vaccine in pregnant women. Therefore, Trumenba should be used during pregnancy only if clearly needed (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Lactation: It is unknown whether Trumenba is excreted in human milk.
Trumenba should only be used during breast-feeding when the possible advantages outweigh the potential risks.
Fertility: Animal studies do not indicate direct or indirect harmful effects with respect to fertility in females (see Pharmacology: Toxicology: Preclinical safety data under Actions).

The safety of Trumenba was investigated in clinical studies that enrolled over 23,000 subjects, of which approximately 17,000 subjects received at least one dose of Trumenba administered alone or concomitantly with a licensed vaccine and over 6,000 control subjects received either saline alone, a licensed vaccine alone, or saline and a licensed vaccine.
Adverse reactions reported in clinical studies are listed in this section per system organ class, in decreasing order of seriousness.
Adverse reactions following booster vaccination in 301 subjects aged 15 to 23 years were similar to adverse reactions during the primary Trumenba vaccination series approximately 4 years earlier. (See Table 8.)

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Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Trumenba can be given concomitantly with any of the following vaccines: Reduced Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis and Inactivated Poliovirus Vaccine (dTaP-IPV), Quadrivalent Human Papillomavirus vaccine (HPV4), Meningococcal Serogroups A, C, W, Y conjugate vaccine (MenACWY) and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap).
Do not mix Trumenba with other vaccines or products in the same syringe.
Individuals with impaired immune responsiveness due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents) may not respond optimally to active immunization with Trumenba.

Incompatibilities: Do not mix Trumenba with other vaccines/products in the same syringe.
Special precautions for disposal and other handling: The vaccine should be shaken vigorously to ensure that a homogeneous white suspension is obtained.
Do not use the vaccine if it cannot be re-suspended.
The vaccine should be visually inspected for particulate matter and discoloration prior to administration. This product should not be used if particulate matter or discoloration is found.
Any unused product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C-8°C).
Syringes should be stored in the refrigerator horizontally to minimize the re-dispersion time.
Do not freeze. Discard if the vaccine has been frozen.

Vaccines, Antisera & Immunologicals

J07AH09 - meningococcus B, multicomponent vaccine ; Belongs to the class of meningococcal bacterial vaccines.

POM