Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine Administered to Healthy Adolescents According to Different Vaccination Schedules

Study Overview
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Brief Summary
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The proposed study is aimed to assess the antibody response and short-term persistence of Novartis Meningococcal B Vaccine after one, two or three doses and to evaluate the optimal vaccination schedule in an adolescent population.

Official Title
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A Phase 2b/3, Multi-Center, Observer-Blind, Controlled Study of the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine Administered to Healthy Adolescents Aged 11-17 Years According to Different Vaccination Schedules

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: rMenB+OMV NZ
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1)11-17 years of age inclusive who have given their written assent and whose parents or legal guardians have given written informed consent at the time of enrollment; 2)who are available for all the visits scheduled in the study (i.e., not planning to leave the area before the end of the study period); 3)in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: History of any meningococcal B vaccine administration; Current or previous, confirmed or suspected disease caused by N. meningitidis; Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment; Significant acute or chronic infection within the previous 7 days or fever (defined as axillary temperature ≥38°C) within the previous day; Antibiotics within 6 days prior to enrollment; Pregnancy or nursing (breastfeeding) mothers; Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the 7 months duration of the study. Oral, injected or implanted hormonal contraceptive, diaphragm, condom, intrauterine device or sexual abstinence are considered acceptable forms of birth control. If sexually active the subject must have been using one of the accepted birth control methods at least two months prior to study entry; Any serious chronic or progressive disease (e.g., neoplasm, diabetes, cardiac disease, hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition). Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, including use of corticosteroids in immunosuppressive doses or chronic use of inhaled high-potency corticosteroids within the previous 60 days. [Use of topical corticosteroids administered during the study in limited areas (i.e., eczema on knees or face or elbows) of the body is allowed]; immunostimulants; Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days; History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component; Receipt of or intent to immunize with any other vaccine(s) within 30 days prior (60 days for live viral vaccines) and throughout the study period (exception: licensed fluvaccine should not be administered within 14 days prior to enrollment; routine vaccine administration may be administered after the blood draw at Study Month 7); Participation in another clinical trial within the last 90 days or planned for during study; Family members and household members of research staff; Any condition which in the opinion of the investigator and/or the Regional MD may interfere with the evaluation of the study objectives.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 17 Years

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 |
| --- | --- |
| Experimental: rMenB06<br>Subjects received one injection of rMenB+OMV NZ vaccine (month 0) and two injections of placebo (at month 1, month 2). A second injection of rMenB+OMV NZ vaccine was given later (month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB0<br>Subjects received one injection of rMenB+OMV NZ vaccine (month 0) and three injections of placebo (month 1, month 2 and month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB016<br>Subjects received two injections of rMenB+OMV NZ vaccine (at month 0 and month 1) and one injection of placebo (at month 2). A third injection of rMenB+OMV NZ vaccine was given later (at month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB01<br>Subjects received two injections of rMenB+OMV NZ vaccine (at month 0 and month 1) and two injection of placebo (at month 2 and month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB026<br>Subjects received two injections of rMenB+OMV NZ vaccine (at month 0 and month 2) and one injection of placebo (at month 2). A third injection of rMenB+OMV NZ vaccine was given later (at month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB02<br>Subjects received two injections of rMenB+OMV NZ vaccine (at month 0 and month 2) and two injections of placebo (at month 1 and month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB012<br>Subjects received three injections of rMenB+OMV NZ vaccine (at month 0, month 1 and month 2) and one injection of placebo later (at month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |
| Experimental: rMenB6<br>Subjects received three injections of placebo(at month 0, month 1 and month 2) and one injection of rMenB+OMV NZ vaccine(at month 6). | Biological: rMenB+OMV NZ<br> <br> * Other names: Serogroup B Meningococcal Vaccine;Biological: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA Titer ≥1:4 After Receiving One, Two or Three Doses of rMenB+OMV NZ Vaccine. | Immunogenicity was evaluated by measuring the percentage of subjects with hSBA titter >1:4 against 44/76-SL, 5/99, NZ98/254 strains at months 1, 2, 3. | Month-1, 2, 3 | 
| Number of Subjects With Local Reactions and Systemic Reactions Occurring in Days 1 to 7 After Vaccination | Safety was assessed as the number of subjects who reported local and systemic reactions during day 1 to day 7 after any vaccination with rMenB+OMV | 1 to 7 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA Titer ≥1:4 After Receiving a Booster Dose of rMenB+OMV NZ Vaccine at Month 6. | Immunogenicity was evaluated by measuring the percentage of subjects with hSBA titter >1:4 agains 44/76-SL, 5/99, NZ98/254 strains at months 6 & 7. | Month-6 & 7 | 
| Percentage of Subjects With hSBA Titer ≥1:8 After Primary and Booster Vaccination. | Immunogenicity was evaluated by measuring the percentage of subjects with hSBA titer ≥1:8 against 44/76-SL, 5/99, NZ98/254 strains. | at baseline, month-1, month-2, month-3, month-6 and month-7. | 
| Percentages of Subjects With at Least a Fourfold Rise in hSBA Titer Over the Prevaccination and After Booster Vaccination. | Immunogenicity was evaluated by measuring the percentage of subjects with at least a fourfold rise in hSBA titer over the prevaccination and after booster vaccination against 44/76-SL, 5/99, NZ98/254 strains at month-1, month-2, month-3 and month-7. | Month-1, month-2, month-3 and month-7 | 
| Geometric Mean Titers (GMTs) After Primary and Booster Vaccination. | Immunogenicity was evaluated by measuring the Geometric mean titers (GMTs) after primary and booster vaccination against 44/76-SL, 5/99, NZ98/254. | month-1, month-2, month-3, month-6 and month-7 | 
| Geometric Mean Ratios (GMRs) After Primary and Booster Vaccination. | Immunogenicity was evaluated by measuring the Geometric mean ratios (GMRs) after primary and booster vaccination against 44/76-SL, 5/99, NZ98/254. | month-1, month-2, month-3, month-6 and month-7 | 
| GMCs of Antibodies Against 287-953Antigen (ELISA) After Primary and Booster Vaccination. | Immunogenicity was evaluated by measuring the Geometric mean Concentration (GMCs) after primary and booster vaccination against Antigen 287-953 Antigen. | month-1, month-2, month-3, month-6 and month-7 | 
| GMRs of Antibodies Against 287-953Antigen (ELISA) After Primary and Booster Vaccination | Immunogenicity was evaluated by measuring the Geometric mean Ratios (GMRs) after primary and booster vaccination against 287-953Antigen | month-1, month-2, month-3, month-6 and month-7 | 
| Number of Subjects Reporting Unsolicited AEs Throughout the Study. | Safety was assessed as the number of subjects who reported unsolicited AEs throughout the study. | Throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal disease, Neisseria meningitidis serogroup B, prevention, vaccination, adolescents