Leaflet TRUMENBA 60mcg / 60mcg suspension for injection in pre-filled syringe
Indicated for: prevention of meningococcal disease
Route of administration: injectable
Substance: meningococcal group B vaccine (recombinant, adsorbed) (vaccine)
ATC: J07AH09 (Antiinfectives for systemic use | Bacterial vaccines | Meningococcal vaccines)
Risk of severe allergic reaction. Seek urgent medical help if serious symptoms occur.
This medicine is subject to additional monitoring.
Store in the refrigerator as instructed in the leaflet.
Store protected from light.
The group B meningococcal vaccine (recombinant, adsorbed) is used to prevent infections caused by Neisseria meningitidis serogroup B, a bacterium that can cause meningitis and septicemia. The vaccine contains recombinant proteins derived from serogroup B, which stimulate the immune system to produce specific antibodies against this serogroup.
The vaccine is administered intramuscularly, usually in two or three doses, depending on the patient's age and the recommended vaccination schedule. It is particularly indicated for infants, adolescents, and individuals at increased risk of infection.
Common side effects include pain at the injection site, fever, fatigue, and irritability. In rare cases, severe allergic reactions may occur.
The group B meningococcal vaccine (recombinant, adsorbed) is an essential preventive measure for reducing the incidence of meningococcal diseases caused by serogroup B, helping to protect vulnerable populations and prevent severe complications associated with these infections.
General data about TRUMENBA 60mcg / 60mcg
- Substance: meningococcal group B vaccine (recombinant, adsorbed)
- Date of latest medicines list: 01-06-2026
- Product code: W65911001
- Concentration: 60mcg / 60mcg
- Pharmaceutical form: suspension for injection in pre-filled syringe
- Packing volume: 0,5 ml
- Product type: Original
- Price: 470.57 RON
- Prescription status: P-RF - Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Leaflet TRUMENBA 60mcg/60mcg
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Contents of the package leaflet for the medicine TRUMENBA 60mcg / 60mcg suspension for injection in pre-filled syringe
1. NAME OF THE MEDICINAL PRODUCT
Trumenba suspension for injection in pre-filled syringe
Meningococcal group B vaccine (recombinant, adsorbed)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 dose (0.5 ml) contains:
Neisseria meningitidis serogroup B fHbp subfamily A1,2,3 60 micrograms
Neisseria meningitidis serogroup B fHbp subfamily B1,2,3 60 micrograms1 Recombinant lipidated fHbp (factor H binding protein)2 Produced in Escherichia coli cells by recombinant DNA technology3 Adsorbed on aluminium phosphate (0.25 milligram aluminium per dose)
Excipients with known effectTrumenba contains 0.018 mg of polysorbate 80 in each 0.5 mL dose, which is equivalent to0.035 mg/mL of polysorbate 80.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Suspension for injection.
White liquid suspension.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Trumenba is indicated for active immunisation of individuals 10 years and older to prevent invasivemeningococcal disease caused by Neisseria meningitidis serogroup B.
See section 5.1 for information on the immune response against specific serogroup B strains.
The use of this vaccine should be in accordance with official recommendations.
4.2 Posology and method of administration
Primary series2 doses: (0.5 ml each) administered at a 6 month interval (see section 5.1).
3 doses: 2 doses (0.5 ml each) administered at least 1 month apart, followed by a third dose at least4 months after the second dose (see section 5.1).
Booster doseA booster dose should be considered following either dosing regimen for individuals at continued riskof invasive meningococcal disease (see section 5.1).
Other paediatric populations
Safety and efficacy of Trumenba in children younger than 10 years of age have not been established.
Currently available data in infants are described in section 4.8 and for children 1 to 9 years of age aredescribed in sections 4.8 and 5.1; however, no recommendation on a posology can be made as data arelimited.
Trumenba should not be used in infants aged 2 to 6 months because of safety concerns (see section4.8).
Method of administrationFor intramuscular injection only. The preferred site for injection is the deltoid muscle of the upperarm.
For instructions on the handling of the vaccine before administration, see section 6.6.
There are no data available on the interchangeability of Trumenba with other meningococcal group Bvaccines to complete the vaccination series.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
In order to improve the traceability of biological medicinal products, the tradename and batch numberof the administered product should be clearly recorded.
HypersensitivityAppropriate medical treatment and supervision should always be readily available in case of ananaphylactic event following the administration of the vaccine.
SyncopeAs with other injectable vaccines, syncope (fainting) can occur in association with administration of
Trumenba. Procedures should be in place to avoid injury from fainting.
Concurrent acute illness
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 ofvaccination.
Intramuscular injections
Trumenba should not be administered intravenously, intradermally, or subcutaneously.
Trumenba should not be given to individuals with thrombocytopenia or any coagulation disorder thatwould contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk ofadministration.
Altered immunocompetence
Immunocompromised individuals, including individuals receiving immunosuppressant therapy, mayhave a diminished immune response to Trumenba. Immunogenicity data are available in individualswith complement deficiencies or splenic dysfunctions (see section 5.1).
Persons with familial complement deficiencies (for example, C5 or C3 deficiencies) and personsreceiving treatments that inhibit terminal complement activation (for example, eculizumab) are atincreased risk for invasive disease caused by Neisseria meningitidis serogroup B, even if they developantibodies following vaccination with Trumenba.
Protection against meningococcal diseaseAs with any vaccine, vaccination with Trumenba may not protect all vaccine recipients.
Limitations of clinical trialsThere are limited data on the use of Trumenba in individuals 40 to 65 years of age and there are nodata on the use of Trumenba in individuals older than 65 years of age.
ExcipientsThis vaccine contains polysorbate 80 (see section 2). Polysorbate 80 may cause hypersensitivityreactions.
This vaccine contains less than 1 mmol sodium (23 mg) per dose. Individuals on low sodium diets canbe informed that this vaccine is essentially sodium-free.
4.5 Interaction with other medicinal products and other forms of interaction
Trumenba can be given concomitantly with any of the following vaccines: Tetanus Toxoid, Reduced
Diphtheria Toxoid, Acellular Pertussis, and Inactivated Poliovirus Vaccine (TdaP-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).
When given concomitantly with other vaccines Trumenba must be administered at a separate injectionsite.
Trumenba should not be mixed with other vaccines in the same syringe.
4.6 Fertility, pregnancy and lactation
There are no data from the use of Trumenba in pregnant women. The potential risk for pregnantwomen is unknown. Nevertheless, vaccination should not be withheld when there is a clear risk ofexposure to meningococcal infection.
Reproduction studies performed in female rabbits have revealed no evidence of impaired femalefertility or harm to the foetus due to Trumenba.
Breast-feedingIt is unknown whether Trumenba is excreted in human milk. Trumenba should only be used duringbreast-feeding when the possible advantages outweigh the potential risks.
FertilityAnimal studies do not indicate direct or indirect harmful effects with respect to fertility in females (seesection 5.3).
Trumenba has not been evaluated for impairment of fertility in males.
4.7 Effects on ability to drive and use machines
Trumenba has no or negligible influence on the ability to drive and use machines. However, some ofthe effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.
4.8 Undesirable effects
The safety profile presented is based on analysis of approximately 17,000 subjects (1 year of age andolder) who have been vaccinated with at least 1 dose of Trumenba in completed clinical studies.
In over 16,000 subjects ≥ 10 years of age studied, the most common adverse reactions were headache,diarrhoea, nausea, muscle pain, joint pain, fatigue, chills, and injection site pain, swelling and redness.
Adverse reactions following booster vaccination in 301 subjects 15 to 23 years of age were similar toadverse reactions during the primary Trumenba vaccination series approximately 4 years earlier.
List of adverse reactions
Adverse reactions reported in clinical studies of subjects 10 years of age and older are listed indecreasing order of frequency and seriousness.
Very common (≥ 1/10)
Common (≥ 1/100 to < 1/10)
Uncommon (≥ 1/1,000 to < 1/100)
Rare (≥ 1/10,000 to < 1/1,000)
Very rare (< 1/10,000)
Not known (cannot be estimated from available data)
Immune system disordersNot known: Allergic reactions*
Nervous system disordersVery Common: Headache
Gastrointestinal disordersVery Common: Diarrhoea; nausea
Common: Vomiting
Musculoskeletal and connective tissue disordersVery Common: Muscle pain (myalgia); joint pain (arthralgia)
General disorders and administration site conditionsVery Common: Chills; fatigue; redness (erythema), swelling (induration) and pain at injection site
Common: Fever ≥ 38 °C (pyrexia)
*Reported in the postmarketing experience. Because this reaction was derived from spontaneousreports, the frequency could not be determined and is thus considered as not known.
Paediatric population < 10 years of age
Children/toddlers
In a study of 294 children 2 to 9 years of age, the following adverse reactions occurred at a frequencyof very common (≥ 1/10): headache, diarrhoea, vomiting, muscle pain, joint pain, fever, fatigue, andinjection site pain, swelling and redness. Fever (≥ 38 °C) was reported in 24.5% of subjects.
In a study of 220 toddlers 1 to < 2 years of age, the following adverse reactions occurred at afrequency of very common (≥ 1/10): drowsiness, irritability (fussiness), loss of or decreased appetite,fever, and injection site pain, swelling and redness. Fever (≥ 38 °C) was reported in 37.3% of subjects.
In clinical studies, fever (≥ 38 °C) occurred more frequently as subject age decreased. Fever followeda predictable pattern after vaccination: onset occurred within 2 to 4 days, lasted 1 day, and was mild tomoderate in severity. Fever rate and severity tended to decrease with subsequent Trumenbavaccinations.
Booster vaccination in children
Adverse reactions following a booster vaccination in 147 subjects 3 to 5 years of age were similar toadverse reactions during the primary Trumenba vaccination series approximately 2 years earlier.
Infants less than 1 year of age
In a study including 115 infants 2 months and 48 infants 6 months of age who received Trumenba oran investigational combination meningococcal vaccine containing Trumenba co-administered withvaccines licensed for this age group, the following adverse reactions occurred at a frequency of verycommon (≥ 1/10): drowsiness, irritability (fussiness), loss of or decreased appetite, fever, and injectionsite pain, swelling and redness.
Fever (≥ 38 °C) was reported in 74% of subjects, with 69% of subjects (33 out of 48) 6 months of agereporting fever and 76% of subjects (87 out of 115) 2 months of age. Occurrence of fever> 38.9 °C-40.0 °C was very common (12.0-25.0%) in both age groups, despite the use of paracetamol.
The rate and severity of fever did not decrease with the second vaccination in the youngest infants.
The study was terminated as two infants 2 months of age developed fever (39.3 °C and 39 °C,respectively) after the first vaccination that, despite the use of antipyretics, led to medical attention andinvestigations including lumbar puncture. Cerebrospinal fluid (CSF) analysis showed pleocytosiswithout positive microbiological test results in 1 infant. Both cases were treated as presumedinfections. Symptoms resolved for both infants. Postmarketing data revealed 3 additional cases inwhich infants 1 to 3 months of age experienced fever leading to medical attention and investigationsincluding lumbar puncture 1 day after administration of Trumenba. CSF analysis showed nopleocytosis in 2 cases and in 1 case showed pleocytosis without a positive microbiological test result.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
4.9 Overdose
Experience of overdose is limited. In the event of overdose, monitoring of vital functions and possiblesymptomatic treatment is recommended.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: vaccines; ATC code: J07AH09
Mechanism of actionTrumenba is a vaccine composed of 2 recombinant lipidated factor H binding protein (fHbp) variants.fHbp is found on the surface of meningococcal bacteria and helps bacteria to avoid host immunedefenses. fHbp variants segregate into 2 immunologically distinct subfamilies, A and B, and over 96%of meningococcal serogroup B isolates in Europe express fHbp variants from either subfamily on thebacterial surface.
Immunisation with Trumenba, which contains one fHbp variant each from subfamily A and B, isintended to stimulate the production of bactericidal antibodies that recognise fHbp expressed bymeningococci. The Meningococcal Antigen Surface Expression (MEASURE) assay was developed torelate the level of fHbp surface expression to killing of meningococcal serogroup B strains in serumbactericidal assays with human complement (hSBAs). A survey of over 2,150 different invasivemeningococcal serogroup B isolates collected from 2000-2014 in 7 European countries, the US and
Canada demonstrated that over 91% of all meningococcal serogroup B isolates expressed sufficientlevels of fHbp to be susceptible to bactericidal killing by vaccine-induced antibodies.
Clinical efficacyThe efficacy of Trumenba has not been evaluated through clinical trials. Vaccine efficacy has beeninferred by demonstrating the induction of serum bactericidal antibody responses to 4 meningococcalserogroup B test strains (see the Immunogenicity section). The 4 test strains express fHbp variantsrepresenting the 2 subfamilies (A and B) and, when taken together, are representative ofmeningococcal serogroup B strains causing invasive disease.
ImmunogenicityProtection against invasive meningococcal disease is mediated by serum bactericidal antibodies tobacterial surface antigens. Bactericidal antibodies act in concert with human complement to killmeningococci. This process is measured in vitro with hSBA for meningococcal serogroup B. AnhSBA titre of ≥ 1:4 is assumed to be protective against meningococcal disease. In the immunogenicityanalysis for Trumenba, a more conservative hSBA titre threshold of ≥ 1:8 or 1:16 was applied,depending on the hSBA strain.
Vaccine coverage was investigated using four primary representative meningococcal serogroup B teststrains: two expressing subfamily A fHbp (variants A22 and A56) and two expressing subfamily BfHbp (variants B24 and B44). To support and further extend the breadth of vaccine coverage, anadditional 10 meningococcal serogroup B test strains were used; these included six expressingsubfamily A fHbp (variants A06, A07, A12, A15, A19 and A29) and four expressing subfamily BfHbp (variants B03, B09, B15 and B16).
Immunogenicity in subjects 10 years of age and olderThe immunogenicity of Trumenba described in this section includes results from Phase 2 and Phase 3clinical studies:
- Following the 2-dose schedule (0 and 6 months) in subjects 10 to 25 years of age in the US and
Europe (Study B1971057);
- Following the 3-dose schedule (0, 2, and 6 months) in subjects 10 to 25 years of age globally(Studies B1971009 and B1971016); and
- Following the 2-dose (0 and 6 months) and 3-dose schedules (0, 1-2, and 6 months) in subjects11 to 18 years of age in Europe (Study B1971012).
Study B1971057 is a Phase 3, randomised, active-controlled, observer-blinded, multicentre trial inwhich subjects 10 to 25 years of age received Trumenba at months 0 and 6 (coadministered with
MenACWY-CRM for the first dose) or an investigational pentavalent meningococcal vaccine atmonths 0 and 6. A total of 1,057 subjects received Trumenba and 543 subjects received theinvestigational control. The hSBA titres for primary test strains are presented in Table 1. Table 2presents the hSBA titres against the additional 10 test strains which support and extend the breadth ofvaccine coverage demonstrated by the 4 representative primary strains.
Table 1: hSBA titres among subjects 10 to 25 years of age receiving Trumenba on a 0- and6-month schedule for primary strains 1 month post-dose 2 (Study B1971057)
Composite(4)≥ 4-fold rise(1) Titre ≥ 1:8(2) GMT(3)
Pre-vaccination 1 Post-dose 2% % GMT N % N %
N N
Strain (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)73.8 91.0 49.3
A22 827 852(70.6, 76.7) (88.8, 92.8) (46.2, 52.6)95.0 99.4 139.5
A56 823 854(93.3, 96.4) (98.6, 99.8) (130.6, 149.1) 1.8 74.3799 81467.4 79.3 21.2 (1.0, 2.9) (71.2, 77.3)
B24 835 842(64.1, 70.6) (76.4, 82.0) (19.6, 22.9)86.4 94.5 37.8
B44 850 853(83.9, 88.6) (92.7, 95.9) (35.1, 40.8)
Abbreviations: GMT=geometric mean titre; hSBA=serum bactericidal assay using human complement.(1) A ≥ 4-fold rise is defined as (i) A hSBA titre ≥ 1:16 for subjects with a baseline hSBA titre < 1:4. (ii) Four times the 1:8or 16 threshold or four times the baseline hSBA titre, whichever is higher for subjects with a baseline hSBA titre ≥ 1:4.(2) All strains used a 1:8 titre threshold except A22 which was 1:16.(3) N for GMT is the same as that presented in preceding titre ≥ 1:8 or 16 column.(4) Proportion of subjects with a composite of hSBA titres ≥ 1:8 or 16 for all four primary strains combined.
Table 2: hSBA titres among subjects 10 to 25 years of age receiving Trumenba on a 0- and6-month schedule for additional strains 1 month post-dose 2 (Study B1971057)
N % titre ≥ 1:8(1) 95% CI
A06 159 89.3 83.4, 93.6
A07 157 96.8 92.7, 99.0
A12 157 83.4 76.7, 88.9
A15 165 89.1 83.3, 93.4
A19 167 90.4 84.9, 94.4
A29 166 95.2 90.7, 97.9
B03 164 74.4 67.0, 80.9
B09 166 71.1 63.6, 77.8
B15 167 85.0 78.7, 90.1
B16 164 77.4 70.3, 83.6
Table 2: hSBA titres among subjects 10 to 25 years of age receiving Trumenba on a 0- and6-month schedule for additional strains 1 month post-dose 2 (Study B1971057)
N % titre ≥ 1:8(1) 95% CI
Abbreviations: hSBA=serum bactericidal assay using human complement.(1) All strains used a 1:8 titre threshold except A06, A12 and A19 which were 1:16.
Study B1971009 was a Phase 3, randomised, active-controlled, observer-blinded, multicentre trial inwhich subjects 10 to 18 years of age received 1 of 3 lots of Trumenba or the active control hepatitis Avirus (HAV) vaccine/saline (control). A total of 2,693 subjects received at least 1 dose of Trumenbaand 897 received at least 1 dose of HAV vaccine/saline. 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 titres for primary test strains observed after the third dose in lot 1and the control are presented in Table 3. Results from lots 2 and 3 are not presented, as only2 representative strains were evaluated. Similar results were observed for lots 2 and 3 as observed forlot 1.
Study B1971016 was a Phase 3, randomised, placebo-controlled, observer-blinded, multicentre trial inwhich subjects 18 to 25 years of age were assigned to receive either Trumenba at months 0, 2, and 6 orsaline at months 0, 2, and 6 in a 3:1 ratio. A total of 2,471 subjects received Trumenba and 822received saline. The hSBA titres for primary test strains observed after the third dose are presented in
Table 3.
Table 3. hSBA titres among subjects 10 to 25 years of age 1 month post-dose 3 of Trumenba or controlon a 0-, 2-, and 6-month schedule for primary strains (Study B1971009 and Study B1971016)
Study B1971009 Study B1971016(10-18 years of age) (18-25 years of age)
Trumenba HAV/saline Trumenba Saline% or GMT % or GMT % or GMT % or GMT
Strain N N N N(95% CI) (95% CI) (95% CI) (95% CI)83.2 9.6 80.5 6.3≥ 4-fold rise(1) 1225 730 1695 568(81.0, 85.2) (7.6, 12.0) (78.6, 82.4) (4.5, 8.7)97.8 34.0 93.5 36.6
A22 hSBA ≥ 1:16 1266 749 1714 577(96.8, 98.5) (30.7, 37.6) (92.2, 94.6) (32.6, 40.6)86.8 12.6 74.3 13.2hSBA GMT 1266 749 (12.0, 13.4) 1714 577(82.3, 91.5) (70.2, 78.6) (12.4, 14.1)90.2 11.3 90.0 10.3≥ 4-fold rise(1) 1128 337 1642 533(88.4, 91.9) (8.1, 15.1) (88.4, 91.4) (7.9, 13.2)99.5 27.5 99.4 34.2hSBA ≥ 1:8 1229 363 1708 552
A56 (98.9, 99.8) (23.0, 32.5) (98.9, 99.7) (30.3, 38.4)176.7222.5 8.8 9.1hSBA GMT 1229 363 1708 (167.8, 552(210.1, 235.6) (7.6, 10.1) (8.2, 10.1)186.1)79.8 2.7 79.3 5.5≥ 4-fold rise(1) 1235 752 1675 562(77.4, 82.0) (1.6, 4.1) (77.3, 81.2) (3.8, 7.7)87.1 7.0 95.1 30.2
B24 hSBA ≥ 1:8 1250 762 1702 573(85.1, 88.9) (5.3, 9.0) (93.9, 96.0) (26.5, 34.1)24.1 4.5 49.5 7.2hSBA GMT 1250 762 1702 573(22.7, 25.5) (4.4, 4.7) (46.8, 52.4) (6.6, 7.8)(1) 85.9 1.0 79.6 1.6≥ 4-fold rise 1203 391 1696 573(83.8, 87.8) (0.3, 2.6) (77.6, 81.5) (0.7, 3.0)
B4489.3 5.3 87.4 11.4hSBA ≥ 1:8 1210 393 1703 577(87.4, 90.9) (3.3, 8.1) (85.8, 89.0) (9.0, 14.3)
Table 3. hSBA titres among subjects 10 to 25 years of age 1 month post-dose 3 of Trumenba or controlon a 0-, 2-, and 6-month schedule for primary strains (Study B1971009 and Study B1971016)
Study B1971009 Study B1971016(10-18 years of age) (18-25 years of age)
Trumenba HAV/saline Trumenba Saline% or GMT % or GMT % or GMT % or GMT
Strain N N N N(95% CI) (95% CI) (95% CI) (95% CI)50.9 4.4 47.6 4.8hSBA GMT 1210 393 1703 577(47.0, 55.2) (4.2, pct. 4.6) (44.2, 51.3) (4.6, 5.1)
Composite(2)1.1 2.0 7.3 6.1
Pre-vaccination 1 1088 354 1612 541(0.6, 1.9) (0.8, 4.0) (6.0, 8.6) (4.2, 8.5)83.5 2.8 84.9 7.5
Post-dose 3 1170 353 1664 535(81.3, 85.6) (1.4, 5.1) (83.1, 86.6) (5.4, 10.0)
Abbreviations: GMT=geometric mean titre; hSBA=serum bactericidal assay using human complement; HAV=hepatitis A virusvaccine.(1) A ≥ 4-fold rise is defined as (i) A hSBA titre ≥ 1:16 for subjects with a baseline hSBA titre < 1:4. (ii) Four times the 1:8/16threshold or four times the baseline hSBA titre, whichever is higher for subjects with a baseline hSBA titre ≥ 1:4.(2) Proportion of subjects with a composite of hSBA titres ≥ 1:8 or 16 for all four primary strains combined.
In Studies B1971009 and B1971016, the proportion of subjects achieving a hSBA titre ≥ 1:8 (variants
A07, A15, A29, B03, B09, B15, B16) or 1:16 (variants A06, A12, A19) against the 10 additional teststrains after 3 doses of Trumenba, administered on a 0-, 2-, and 6-month schedule, was determined.
Across the two studies, the majority of subjects, ranging from 71.3% to 99.3% for the 6 subfamily AfHbp strains and 77.0% to 98.2% for the 4 subfamily B fHbp strains, achieved a hSBA titre ≥ 1:8 or16, consistent with the results observed with the 4 primary test strains.
In Study B1971012, a Phase 2 study in subjects 11 to 18 years of age in Europe, hSBA titres followingcompletion of two 3-dose schedules (0, 1, and 6 months and 0, 2, and 6 months) and a 2-dose schedule(0 and 6 months) were determined against the 4 primary test strains. At 1 month after the third dose,similar robust and broad immune responses were observed for both 3-dose schedules with 86.1% to99.4% achieving hSBA titres ≥ 1:8 or 16 and 74.6% to 94.2% achieving a 4-fold increase in hSBAtitre. At 1 month after completion of the 2-dose schedule (0 and 6 months), 77.5% to 98.4% achievedhSBA titres ≥ 1:8 or 16 and 65.5% to 90.4% achieved a 4-fold increase in hSBA titre.
Study B1971033 was an open-label, follow-up study of subjects previously enrolled in a primarystudy, including Study B1971012. Subjects attended visits over 4 years for collection of blood samplesand received a single booster dose of Trumenba approximately 4 years after receipt of a primary seriesof 2 or 3 doses of Trumenba. hSBA titres 4 years after the primary series and 26 months after thebooster dose for subjects enrolled from primary Study B1971012 Group 1 (0, 1, and 6 months),
Group 2 (0, 2, and 6 months), and Group 3 (0 and 6 months) are presented in Table 4. A boosterresponse was observed as measured by hSBA at 1 month following a dose of Trumenba approximately4 years after a primary series of 2 doses (Group 3) or 3 doses (Groups 1 and 2).
Table 4: hSBA titres among subjects 11 to 18 years of age receiving Trumenba on a 0-, 1-, 6-month; 0-, 2-,and 6-month; and 0- and 6-month schedules and a booster 4 years after primary seriescompletion (Study B1971033)
Primary Study B1971012 Vaccine Groups (as Randomised)0, 1, and 6 months 0, 2, and 6 months 0 and 6 months% ≥ 1:8(1) GMT % ≥ 1:8(1) GMT % ≥ 1:8(1) GMT
Strain Timepoint N (95% CI) (95% CI) N (95% CI) (95% CI) N (95% CI) (95% CI)89.8 53.0 91.2 59.5 98.4 55.8month 1 59 57 61(79.2, 96.2) (40.4, 69.6) (80.7, 97.1) (45.5, 77.8) (91.2, 100.0) (46.2, 67.4)
A2241.4 14.9 45.0 15.8 36.3 15.6month 12 99 111 113(31.6, 51.8) (12.6, 17.7) (35.6, 54.8) (13.4, 18.6) (27.4, 45.9) (13.0, 18.8)
Post-primary
Table 4: hSBA titres among subjects 11 to 18 years of age receiving Trumenba on a 0-, 1-, 6-month; 0-, 2-,and 6-month; and 0- and 6-month schedules and a booster 4 years after primary seriescompletion (Study B1971033)
Primary Study B1971012 Vaccine Groups (as Randomised)0, 1, and 6 months 0, 2, and 6 months 0 and 6 months% ≥ 1:8(1) GMT % ≥ 1:8(1) GMT % ≥ 1:8(1) GMT
Strain Timepoint N (95% CI) (95% CI) N (95% CI) (95% CI) N (95% CI) (95% CI)49.2 16.6 56.1 20.7 55.7 16.6month 48 59 57 61(35.9, 62.5) (13.0, 21.1) (42.4, 69.3) (15.6, 27.4) (42.4, 68.5) (13.4, 20.5)100.0 126.5 100.0 176.7 96.7 142.0month 1 59 58 60(93.9, 100.0) (102.7, 155.8) (93.8, 100.0) (137.8, 226.7) (88.5, 99.6) (102.9, 196.1)74.1 33.6 77.8 44.1 80.0 31.6month 12 58 54 60(61.0, 84.7) (24.5, 46.1) (64.4, 88.0) (31.2, 62.4) (67.7, 89.2) (23.5, 42.5)(2) (2) 73.5 34.7 61.9 27.1month 26 0 NE NE 34 42(55.6, 87.1) (23.0, 52.4) (45.6, 76.4) (18.6, 39.6)100.0 158.7 98.2 191.2 98.4 143.1month 1 58 57 62(93.8, 100.0) (121.5, 207.3) (90.6, 100.0) (145.8, 250.8) (91.3, 100.0)(109.6, 187.0)73.5 25.7 76.1 27.3 60.4 18.5month 12 98 109 106(63.6, 81.9) (19.4, 34.0) (67.0, 83.8) (21.0, 35.4) (50.4, 69.7) (13.8, 24.7)43.4 10.7 56.4 15.0 43.5 10.8month 48 53 55 62(29.8, 57.7) (7.4, 15.3) (42.3, 69.7) (10.2, 22.2) (31.0, 56.7) (7.6, 15.3)
A56100.0 359.8 100.0 414.8 98.4 313.1month 1 57 56 62(93.7, 100.0) (278.7, 464.7) (93.6, 100.0) (298.8, 575.9) (91.3, 100.0)(221.3, 442.8)90.9 47.3 89.1 64.0 81.4 41.0month 12 55 55 59(80.0, 97.0) (34.3, 65.3) (77.8, 95.9) (42.6, 96.2) (69.1, 90.3) (26.7, 62.7)month 26 0 NE(2) (2) 82.8 37.8 57.5 16.0
NE 29 40(64.2, 94.2) (21.3, 67.2) (40.9, 73.0) (9.9, 25.8)88.1 25.6 91.4 30.5 85.0 29.2month 1 59 58 60(77.1, 95.1) (19.7, 33.3) (81.0, 97.1) (23.8, 39.1) (73.4, 92.9) (21.5, 39.6)40.8 9.7 49.1 11.5 36.9 8.4month 12 98 108 103(31.0, 51.2) (7.5, 12.4) (39.3, 58.9) (9.0, 14.6) (27.6, 47.0) (6.7, 10.6)40.7 10.7 49.1 11.4 40.3 8.9month 48 59 57 62(28.1, 54.3) (7.6, 15.1) (35.6, 62.7) (8.2, 15.9) (28.1, 53.6) (6.8, 11.8)
B24100.0 94.9 100.0 101.6 96.8 79.1month 1 58 57 62(93.8, 100.0) (74.6, 120.9) (93.7, 100.0) (83.1, 124.2) (88.8, 99.6) (60.6, 103.5)65.5 21.1 74.1 25.7 77.4 22.4month 12 58 54 62(51.9, 77.5) (14.2, 31.3) (60.3, 85.0) (17.7, 37.5) (65.0, 87.1) (16.4, 30.5)(2) (2) 78.8 24.4 59.5 14.5month 26 0 NE NE 33 42(61.1, 91.0) (16.1, 36.8) (43.3, 74.4) (9.9, 21.3)86.2 46.3 89.5 50.2 60 81.7 35.5month 1 58 57(74.6, 93.9) (31.7, 67.8) (78.5, 96.0) (35.3, 71.3) (69.6, 90.5) (24.5, 51.4)24.0 6.4 22.5 6.0 16.5 5.6month 12 100 111 115(16.0, 33.6) (5.2, 7.8) (15.1, 31.4) (5.1, 7.2) (10.3, 24.6) (4.8, 6.5)36.8 8.3 35.1 7.6 12.9 4.6month 48 57 57 62(24.4, 50.7) (6.3, 11.0) (22.9, 48.9) (5.8, 10.0) (5.7, 23.9) (4.1, 5.1)
B44100.0 137.3 100.0 135.9 93.4 74.2month 1 59 58 61(93.9, 100.0) (100.3, 188.0) (93.8, 100.0) (108.0, 171.0) (84.1, 98.2) (51.6, 106.8)75.0 23.2 81.1 24.3 59.0 13.3month 12 56 53 61(61.6, 85.6) (16.2, 33.2) (68.0, 90.6) (17.8, 33.3) (45.7, 71.4) (9.7, 18.3)66.7 16.0 62.8 13.6month 26 0 NE(2) NE(2) 33 43(48.2, 82.0) (10.4, 24.7) (46.7, 77.0) (9.8, 18.9)
Composite(3)80.7 87.3 77.2month 1 57 NE 55 NE 57 NE(68.1, 90.0) (75.5, 94.7) (64.2, 87.3)
Post- Post-booster Post-primary Post-booster Post-primary Post-booster Post-primary Post-booster
Table 4: hSBA titres among subjects 11 to 18 years of age receiving Trumenba on a 0-, 1-, 6-month; 0-, 2-,and 6-month; and 0- and 6-month schedules and a booster 4 years after primary seriescompletion (Study B1971033)
Primary Study B1971012 Vaccine Groups (as Randomised)0, 1, and 6 months 0, 2, and 6 months 0 and 6 months% ≥ 1:8(1) GMT % ≥ 1:8(1) GMT % ≥ 1:8(1) GMT
Strain Timepoint N (95% CI) (95% CI) N (95% CI) (95% CI) N (95% CI) (95% CI)10.9 13.7 20.4month 12 55 NE 51 NE 49 NE(4.1, 22.2) (5.7, 26.3) (10.2, 34.3)19.6 30.2 9.8month 48 51 NE 53 NE 61 NE(9.8, 33.1) (18.3, 44.3) (3.7, 20.2)100 100.0 91.5month 1 56 NE 55 NE 59 NE(93.6, 100.0) (93.5, 100.0) (81.3, 97.2)52.8 64.6 61.4month 12 53 NE 48 NE 57 NE(38.6, 66.7) (49.5, 77.8) (47.6, 74.0)(2) 48.1 44.4month 26 0 NE NE 27 NE 36 NE(28.7, 68.1) (27.9, 61.9)
Abbreviations: hSBA=serum bactericidal assay using human complement; NE=not evaluated; GMT=geometric mean titre.(1) All strains used a 1:8 titre threshold except A22 which was 1:16.(2) Subjects were not followed beyond 12 months post booster.(3) Proportion of subjects with a composite of hSBA titres ≥ 1:8 or 16 for all four primary strains combined.
Serum samples were analysed concurrently in the same serology campaign for all time points except the 12 months post-primary dose timepoint for which results are from the interim analysis.
Immunogenicity in special populations
Individuals 10 years of age and above with complement deficiencies or splenic dysfunction
Study B1971060 was a Phase 4 study in which 53 participants ≥ 10 years of age with anatomic orfunctional asplenia (N=51) or complement deficiency (N=2) received Trumenba at months 0 and 6,and safety and immunogenicity were compared to historical data from 53 age- and sex-matchedhealthy controls that received Trumenba on the same schedule. The proportions of subjects with hSBAtitres ≥ 1:8 or 16 against the 4 primary test strains after 2 doses of Trumenba 1 month after the secondvaccination are presented in Table 5.
Table 5. hSBA titres among immunocompromised subjects ≥ 10 years of age receiving Trumenbaon a 0- and 6-month schedule for primary strains 1 month post-dose 2 (Study B1971060),compared to controls (Study B1971057)
Study B1971060 Study B1971057(immunocompromised subjects (historical age- and sex-matched≥ 10 years of age) healthy controls)(1)1 month 1 month
Pre-vaccination 1 post-dose 2 Pre-vaccination 1 post-dose 2% ≥ 1:8(2) % ≥ 1:8(2) % ≥ 1:8(2) % ≥ 1:8(2)
Strain N N N N(95% CI) (95% CI) (95% CI) (95% CI)32.6 75.0 31.0 95.3
A22 43 44 42 43(19.1, 48.5) (59.7, 86.8) (17.6, 47.1) (84.2, 99.4)25.6 90.9 23.3 100.0
A56 43 44 43 44(13.5, 41.2) (78.3, 97.5) (11.8, 38.6) (92.0, 100.0)2.4 70.5 23.3 81.8
B24 42 44 43 44(0.1, 12.6) (54.8, 83.2) (11.8, 38.6) (67.3, 91.8)9.3 79.1 11.4 92.9
B44 43 43 44 42(2.6, 22.1) (64.0, 90.0) (3.8, 24.6) (80.5, 98.5)
Abbreviations: hSBA=serum bactericidal assay using human complement; N=number of participants with valid and determinatehSBA titres for the given strain.(1) Healthy controls included subjects ≥ 10 to 25 years of age.(2) All strains used a 1:8 titre threshold except A22 which was 1:16.
Post-booster
Immunogenicity in individuals 1 to 9 years of ageThe immunogenicity of Trumenba (0-, 2- and 6-month schedule) in toddlers and children 1 to 9 yearsof age was evaluated in 2 Phase 2 studies. At 1 month following series completion, 81.4% to 100% ofsubjects achieved a defined hSBA titre threshold against the 4 primary meningococcal test strains(defined as hSBA ≥ 1:16 for A22; ≥ 1:8 for A56, B24 and B44) compared to 0.4% to 6.5% at baseline.
Persistence data following primary series completion in toddlers 1 to < 2 years of age indicate that12.4%, 59.1%, 10.3%, and 40.4% at 6 months and 3.7%, 22.8%, 3.7%, and 12.5% at 24 months afterseries completion maintained hSBA titres ≥ 1:8 or 1:16 against the primary test strains A22, A56, B24and B44, respectively. An anamnestic response was observed when these children received a boosterdose at approximately 24 months after primary series completion at 3 to 5 years of age, with 92.6% to100.0% achieving hSBA titres ≥ 1:8 or 1:16 against the 4 primary strains.
In children 2 to 9 years of age, 6 months following series completion, 32.5%, 82.4%, 15.5% and10.4% of participants maintained hSBA titres ≥ 1:8 or 1:16 against the primary test strains A22, A56,
B24 and B44, respectively. There are no persistence data beyond 6 months or booster dose data in thisage group.
See section 4.2 for information on use in children 1 to 9 years of age.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-clinical data revealed no special hazard for humans based on conventional studies of repeateddose toxicity and reproduction and developmental toxicity.
6 PHARMACEUTICAL PARTICULARS
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Chloride
Histidine
Polysorbate 80 (E433)
Water for injections
For adsorbent, see section 2.
6.2 Incompatibilities
Do not mix Trumenba with other vaccines or medicinal products in the same syringe.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.
6.3 Shelf life
5 years.
6.4 Special precautions for storage
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.
6.5 Nature and contents of container
0.5 ml suspension in a pre-filled syringe (Type I glass) with plastic Luer Lok adapter, chlorobutylrubber plunger stopper, and a synthetic isoprene bromobutyl rubber tip cap with a plastic rigid tip capcover with or without needle. The tip cap and rubber plunger of the pre-filled syringe are not madewith natural rubber latex.
Pack sizes of 1, 5, and 10 pre-filled syringes, with or without needle.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
During storage, a white deposit and clear supernatant may be observed in the pre-filled syringecontaining the suspension.
Before use, the pre-filled syringe should be shaken vigorously to ensure that a homogeneous whitesuspension 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 toadministration. In the event of any foreign particulate matter and/or variation of physical aspect beingobserved, do not administer the vaccine.
Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency https://www.ema.europa.eu.