Safety and Immunogenicity in Dose-Ranging and Formulation-Finding Meningococcal B (MenB) Vaccine Study in 2-month-old Infants

Study Overview
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Brief Summary
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This study is aimed at assessing the safety and immunogenicity of different doses and formulations of a new Novartis Meningococcal B Recombinant Vaccine.

Official Title
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A Phase 2 Partially Observer-Blind Randomized Controlled Multicenter Dose-Ranging and Formulation-Finding Study of a New Novartis Meningococcal B Recombinant Vaccine Evaluating the Safety and Immunogenicity When Given Concomitantly With Routine Vaccines in 2-month-old Infants

Conditions
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Meningococcal Meningitis, Meningococcal Infections

Intervention / Treatment
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* Biological: Meningococcal B vaccine
* Biological: Meningococcal B vaccine
* Biological: Meningococcal B vaccine
* Biological: Meningococcal B vaccine
* Biological: Meningococcal B vaccine
* Biological: Meningococcal B vaccine
* Biological: Control
* Biological: Meningococcal B vaccine with antipyretic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 2-month old infants (55-89 days, inclusive), born after full term pregnancy, gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg Available for all the visits scheduled in the study and for whom a parent/legal guardian is willing/able to comply with all protocol requirements Exclusion Criteria: Any meningococcal B or C vaccine administration Prior vaccination with any Diphtheria, Tetanus, Pertussis (acellular or whole cell), Polio (either Inactivated or Oral), Haemophilus influenzae type b (Hib), and Pneumococcal antigens; Any ascertained or suspected disease caused by N. meningitidis Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis History of severe allergic reaction after previous vaccinations Recent significant acute or chronic infection Oral or parenteral antibiotic treatment in the 7 days prior to the scheduled blood draw; Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic disease, progressive neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition) Any impairment/alteration of the immune system resulting from (for example): Receipt of any immunosuppressive therapy at any time since birth Receipt of immunostimulants at any time since birth Use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids at any time since birth Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation Participation in another clinical trial Family members and household members of research staff History of seizure Any contraindication to paracetamol

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 89 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Vaccine candidate formulation I | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation I<br>|
| Other: 2<br>Vaccine candidate formulation II | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation II<br>|
| Other: 3<br>Vaccine candidate formulation III | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation III<br>|
| Other: 4<br>Vaccine candidate formulation IV | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation IV<br>|
| Other: 5<br>Vaccine candidate formulation V | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation V<br>|
| Other: 6<br>Vaccine candidate formulation VI | Biological: Meningococcal B vaccine<br>* Vaccine candidate formulation VI<br>|
| Other: 7<br>Control | Biological: Control<br>* Control<br>|
| Other: 8<br>Vaccine candidate formulation I with antipyretic | Biological: Meningococcal B vaccine with antipyretic<br>* Vaccine candidate formulation I with antipyretic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Serum Bactericidal Activity (hSBA) ≥ 1:5 at 1 Month After Third Vaccination | To assess the immunogenicity of seven different formulations of 4CMenB (groups I-VI and VIII) given to healthy infants at 2,3 and 4 months of age as measured by percentages of subjects with serum bactericidal activity (SBA) titer≥1:5 against 44/76-SL, 5/99 and NZ98/254 reference strains, at 1 month after the third vaccination.. The analysis was done on the Per Protocol Primary Population at one month after third injection. | At baseline (pre-vaccination) and 30 days after the third vaccination. | 
| Number of Subjects With Fever ≥ 38.5 °C (Rectal Temperature) Within 3 Days (Day 1-3) After First Vaccination | To assess if any of six different formulations of vaccine groups (Group II to Group VI, Group VIII) reduced the incidence of fever >=38.5C (rectal) occurring within three days (day 1-day3) following first vaccination. The analysis was done on the Safety Population. | Day 1 to day 3 after first vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Bactericidal Titers (GMTs), One Month After Third and Booster Vaccination (Men B at 12 Months of Age) | ToTo assess the immune response of seven different formulations of meningococcal multi-component recombinant, adsorbed vaccine (rMenB+OMV NZ or rMenB (no OMV)) in healthy toddlers as measured by SBA geometric mean titers (GMTs) at: One month after third vaccination. One month after booster vaccination (Men B at 12 months of age). | At baseline (pre-vaccination), 30 days after the third vaccination, at booster Baseline and at booster vaccination (12 months of age) | 
| Geometric Mean Bactericidal Titers,One Month After Primary and Booster Vaccination (Men B at 12 Months of Age) | To compare the antibody response of meningococcal multi-component recombinant, adsorbed vaccine (formulation I vs. formulation VIII) and of routine infant vaccine given with or without prophylactic administration of paracetamol medication in healthy toddlers. | At Baseline (pre-vaccination), at 30 days after the third vaccination, at booster Baseline, at 30 days | 
| Geometric Mean Ratios, One Month After Primary and Booster Vaccination (Men B at 12 Months of Age) | To compare the antibody response between meningococcal multi-component recombinant adsorbed vaccine (formulation I) and routine infant vaccine group along with meningococcal multi-component recombinant adsorbed vaccine with prophylactic administration of paracetamol medication as measured by Geometric Mean Ratios (GMRs). | After the third and the booster vaccination. | 
| Percentage of Subjects With hSBA≥1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (Pre-fourth Dose) | To assess the persistence of bactericidal antibodies at 12 months of age after primary vaccination - three doses of one of the seven different formulations of rMenB+OMV NZ or rMenB (no OMV) (Group I-VI and VIII) and rMenB+OMV NZ with paracetamol medication. | 12 months (pre-fourth vaccination) | 
| Percentage of Subjects With hSBA≥1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (One Month-post Fourth Dose) | To assess if any of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (groups I-VI and VIII) induced sufficient immune response when given to healthy toddlers at 12 months of age, as measured by percentage of subjects with SBA titer ≥ 1:5, at 1 month after the fourth vaccination. | 1 month after fourth vaccination | 
| Geometric Mean Bactericidal Titers, After Primary and Booster Vaccinations (Men B at 12 Months of Age) | To assess the induction of immunological memory of three doses of meningococcal multi-component recombinant, adsorbed vaccine by comparing the serum bactericidal antibodies Geometric Mean Bactericidal Titers (GMTs) response in healthy toddlers administered the fourth dose at 12 months of age to the response in meningococcal B vaccine naive toddlers (Group VII) receiving the first dose of meningococcal multi-component recombinant, adsorbed vaccine at 12 months of age. | At 13 months | 
| Percentage of Subjects With hSBA ≥1:5, First Dose of Meningococcal B Vaccine (One Month After Booster) | To assess the immune response of first dose of meningococcal multi-component recombinant, adsorbed vaccine given at 12 months of age to toddlers who previously received three doses of MenC-CRM197 vaccine as infants (group VII). | 1 month after booster | 
| Safety and Reactogenicity of Study Vaccines Within 7 Days After Second and Third Vaccination | To assess if any of six different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (Group II to VI, Group VIII) reduced the incidence of fever ≥ 38.5ºC (rectal) occurring within 3 days (day 1-3) following second and third vaccination and 7 days (day 1-7) following each vaccination as compared to rMenB+OMV NZ (Group I). | Day 1 through day 7 after second and third vaccination. | 
| Number of Subjects With Solicited Local Reactions Within 7 Days (Day 1-7) After Each Vaccination | To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting solicited local reactions within 7 days (day 1-7) after each vaccination. | Day 1 through day 7 after each vaccination. | 
| Number of Subjects With Solicited Systemic Reactions Within 7 Days (Day 1-7) After Each Vaccination | To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting solicited systemic reactions within 7 days (day 1-7) after each vaccination. | Day 1 through day 7 after each vaccination. | 
| Number of Subjects With Unsolicited Adverse Events Within 7 Days (Day 1-7) After Each Vaccination | To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting unsolicited Adverse Events (AEs), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (throughout the study period) within 7 days (day 1-7) after each vaccination. | Day 1 through day 7 after each vaccination. | 
| Number of Subjects With Severe Adverse Events and Adverse Events Necessitating a Medical Office or Emergency Room (ER) Visit and/or Resulting in Premature Withdrawal of the Subject From the Study, Throughout the Study Period. | To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting Severe Adverse Events (SAEs) and Adverse Events (AEs) necessitating a medical office or Emergency Room (ER) visit and/or resulting in premature withdrawal of the subject from the study, throughout the study period. | Overall study period. | 
| Number of Subjects With Local and Systemic Reactions Within 7 Days (Day 1-7) After Second rMenB+OMV NZ Vaccination in MenC Group | To assess the safety and tolerability of two doses of rMenB+OMV NZ vaccine (Group VII) given at 12 and 13 months of age to toddlers who previously received three doses of Menjugate as infants. | Day 1 through day 7 at 13 months age. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Meningitis, Antibody, Infants