TRUMENBA- neisseria meningitidis serogroup b recombinant lp2086 a05 protein variant antigen and neisseria meningitidis serogroup b recombinant lp2086 b01 protein variant antigen injection, suspension
Wyeth Pharmaceutical Division of Wyeth Holdings LLC, a subsidiary of Pfizer Inc.
1 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.
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.
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 months.
Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months.
The choice of dosing schedule may depend on the risk of exposure and the patient's susceptibility to meningococcal serogroup B disease.
2.2 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.
2.3 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.
3 DOSAGE FORMS AND STRENGTHS
Trumenba is a suspension for intramuscular injection in 0.5 mL single-dose prefilled syringe.
4 CONTRAINDICATIONS
Severe allergic reaction after a previous dose of Trumenba.
5 WARNINGS AND PRECAUTIONS
5.1 Management of Allergic Reactions
Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following administration of Trumenba.
5.2 Altered Immunocompetence
Individuals with altered immunocompetence may have reduced immune responses to Trumenba.
6 ADVERSE REACTIONS
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%).
6.1 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; (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.
DESCRIPTION
Trumenba is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHBP) variants from N. meningitidis serogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively).1 The proteins are individually produced in E. coli. Production strains are grown in defined fermentation growth media to a specific density. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added to the drug substances and is present in the final drug product.
Each 0.5 mL dose contains 60 micrograms of each fHBP variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al3 + as AlPO4 in 10 mM histidine buffered saline at pH 6.0.
12 CLINICAL PHARMACOLOGY
12.1 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.
