Trumenba: Package Insert and Label Information

TRUMENBA- neisseria meningitidis group b recombinant lp2086 a05 protein variant antigen and neisseria meningitidis group b recombinant lp2086 b01 protein variant antigen injection, suspension
Wyeth Pharmaceutical Division of Wyeth Holdings LLC

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.

The effectiveness of the two-dose schedule of Trumenba against diverse N. meningitidis 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. 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 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

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 common 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 early phase studies.

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 15,227 subjects 10 through 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 Australia. A total of 11,333 adolescents (10 through 18 years of age) and 3,894 adults (19 through 25 years of age) received at least one dose of Trumenba. A total of 5,501 subjects 10 through 25 years of age in the control groups received saline placebo and/or one of the following vaccine(s): Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (HPV4) (Merck & Co., Inc.); Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) (Sanofi Pasteur Ltd.); Meningococcal Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine (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 safety evaluation in the clinical 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 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 Reactions

Study 1 was 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 years of age received at least 1 dose of Trumenba on a 0-, 2-, and 6- 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 10 to 14 years age, and 44.4% were 15 to 18 years 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 years of age received at least 1 dose of Trumenba and 822 subjects received saline on a 0-, 2,- and 6- 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.

Tables 1 and 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, respectively.

Local adverse reactions were reported more frequently following Trumenba compared to control (see Tables 1 and 2).

Table 1: Percentages of Subjects 10 to 18 Years of Age (Study 1*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba HAV/Saline Trumenba HAV/Saline Trumenba HAV/Saline
Local Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
*
Study 1: National Clinical Trial (NCT) number NCT01830855.
Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months.
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
§
“Any” is defined as the cumulative frequency of subjects who reported a reaction as “mild”, “moderate”, or “severe” within 7 days of vaccination.
Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Pain
Any § 86.7 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
Redness
Any § 16.2 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
Swelling
Any § 18.0 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
Table 2: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba Saline Trumenba Saline Trumenba Saline
Local Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
*
Study 2: National Clinical Trial (NCT) number NCT01352845.
Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
§
“Any” is defined as the cumulative frequency of subjects who reported a reaction as “mild”, “moderate”, or “severe” within 7 days of vaccination.
Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Pain
Any § 84.2 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
Redness
Any § 13.8 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
Swelling
Any § 15.5 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

In Study 1, mean duration of pain was 2.4 to 2.6 days (range 1–17 days), for redness 2.0 to 2.2 days (range 1–12 days) and for swelling 2.0 to 2.1 days (range 1–21 days) in the combined Trumenba group. In Study 2, mean duration of pain was 2.6 to 2.8 days (range 1–67 days), for redness 2.2 to 2.5 days (range 1–13 days) and for swelling 2.1 to 2.6 days (range 1–70 days) in the Trumenba group.

Tables 3 and 4 present the percentage and severity of reported solicited systemic adverse reactions within 7 days of 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 1*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba HAV/Saline Trumenba HAV/Saline Trumenba HAV/Saline
Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
*
Study 1: National Clinical Trial (NCT) number NCT01830855.
Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months.
Study 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 HAV/saline at Dose 1, Dose 2, and Dose 3, respectively.
§
Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
“Any” is defined as the cumulative frequency of subjects who reported a reaction as “mild”, “moderate”, or “severe” within 7 days of vaccination.
#
Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Þ
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Fever (≥38°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
Vomiting §
Any 3.7 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
Diarrhea #
Any 10.6 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
Headache Þ
Any 51.8 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
Fatigue Þ
Any 54.0 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
Chills Þ
Any 25.3 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)Þ
Any 24.4 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 pain Þ
Any 21.9 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 medication 20.7 10.4 13.6 8.9 12.7 6.8
Table 4: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba Saline Trumenba Saline Trumenba Saline
Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
*
Study 2: National Clinical Trial (NCT) number NCT01352845.
Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
Study 2: Fever (≥38°C): N=2415, 2067, and 1814 for Trumenba at Dose 1, Dose 2, and Dose 3, respectively; N=796, 705, and 621 for saline at Dose 1, Dose 2, and Dose 3, respectively.
§
Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
“Any” is defined as the cumulative frequency of subjects who reported a reaction as “mild”, “moderate”, or “severe” within 7 days of vaccination.
#
Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Þ
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Fever (≥38°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
Vomiting §
Any 2.6 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
Diarrhea #
Any 12.7 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
Headache Þ
Any 43.9 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
Fatigue Þ
Any 50.9 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
Chills Þ
Any 18.1 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)Þ
Any 25.9 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 pain Þ
Any 19.6 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 medication 13.4 8.9 12.3 7.6 12.8 6.6

The frequencies of adverse reactions were highest after the first dose regardless of the schedule. After subsequent doses, the 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 by 269 (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 days 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 within 30 days 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 frequently observed in subjects who received Trumenba than subjects in the control group were injection site pain, fever, and headache.

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