Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to demonstrate the equivalence of rMenB+OMV NZ lot 1 to rMenB+OMV NZ lot 2 when administered to adolescents, as measured by human serum bactericidal activity (hSBA) geometric mean titers (GMTs) against 3 N. meningitidis serogroup B reference strains (H44/76, 5/99, and NZ98/254) and as measured by ELISA geometric mean concentrations (GMCs) against vaccine antigen 287-953, approximately 30 days after a primary vaccination course of two doses administered one month apart.

Detailed Description
-----------------
Novartis will consider this study a success if, at one month following the second vaccination, the two-sided 95% CI of the ratio of the hSBA GMTs for each of 3 serogroup B reference strains (H44/76, 5/99, and NZ98/254) and the two-sided 95% CI of the ratio of the ELISA GMCs against vaccine antigen 287-953 are contained within the interval (0.5, 2.0).

Official Title
-----------------
A Phase 3, Randomized, Comparative, Multicenter Observer-Blind Study Evaluating the Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years

Conditions
-----------------
Meningococcal Disease, Meningococcal Meningitis

Intervention / Treatment
-----------------
* Biological: Serogroup B meningococcal vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects (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 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) in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: History of any serogroup B meningococcal vaccination Current or previous, confirmed or suspected disease caused by N. meningitidis 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 ≥ 38.0 °C) within the previous day Antibiotic use within 3 days (72 hours) 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 2 months duration of the study. If sexually active the subject must have been using one of the accepted birth control methods for at least 30 days prior to study entry Any serious chronic or progressive disease, Known or suspected impairment/alteration of the immune system 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

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenB Lot 1<br>MenB vaccine Lot 1: 2 doses administered 1 month apart | Biological: Serogroup B meningococcal vaccine<br>* All subjects will receive two rMenB+OMV NZ vaccinations one month apart and will be followed for a total of 2 months. Subjects will be randomized to 1 of 2 treatment arms to receive either two doses of rMenB+OMV NZ vaccine Lot 1 or two doses of rMenB+OMV NZ Lot 2. A total of 2 blood samples will be collected (at the first vaccination and 1 month after the 2nd vaccination). An additional blood draw will be collected in a subset of approximately 160 subjects (approximately 80 subjects in Group 1 and approximately 80 subjects in Group 2) at 2 weeks after the second vaccination<br>|
| Active Comparator: MenB Lot 2<br>MenB vaccine Lot 2: 2 doses administered 1 month apart | Biological: Serogroup B meningococcal vaccine<br>* All subjects will receive two rMenB+OMV NZ vaccinations one month apart and will be followed for a total of 2 months. Subjects will be randomized to 1 of 2 treatment arms to receive either two doses of rMenB+OMV NZ vaccine Lot 1 or two doses of rMenB+OMV NZ Lot 2. A total of 2 blood samples will be collected (at the first vaccination and 1 month after the 2nd vaccination). An additional blood draw will be collected in a subset of approximately 160 subjects (approximately 80 subjects in Group 1 and approximately 80 subjects in Group 2) at 2 weeks after the second vaccination<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains. | Consistency of the immune response of the two lots of rMenB+OMV NZ will be assessed at one month after the second vaccination based on the ratio of the vaccine lot hSBA GMTs for each of three serogroup B reference strains (H44/76, 5/99, and NZ98/254) and based on the ratio of Enzyme-linked Immunosorbent Assay (ELISA) GMCs for vaccine antigen 287-953. The equivalence interval will be (0.5, 2.0). | One month after the second vaccination (day 61) | 
| ELISA Geometric Mean Concentration (GMCs) Against Vaccine Antigen 287-953 | The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953. | One month after the second vaccination (day 61) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects in Each Lot With hSBA ≥ 1:5 | The percentage of subjects in each lot with hSBA ≥ 1:5 at one month after the second vaccination for each of the three reference strains (H44/76, 5/99, and NZ98/254) for each vaccine group | One month after the second vaccination (day 61) | 
| Geometric Mean Ratio (GMR) of GMTs Against Each of N. Meningitidis Serogroup B Reference Strains. | The immune response of two different lots of rMenB+OMV NZ against each of N. meningitidis serogroup B test strains is evaluated in terms of GMR between GMTs (1month after the second vaccination vs baseline). | One month after the second vaccination (day 61) | 
| Geometric Mean Ratio (GMR) of ELISA Geometric Mean Concentration (GMCs) Against Antigen 287-953 | The immune response of two different lots of rMenB+OMV NZ against antigen 287-953 is evaluated in terms of GMRs between ELISA GMCs (day 61 vs baseline). | One month after the second vaccination (day 61) | 
| hSBA GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45. | The immunogenicity of two different lots of rMenB+OMV NZ is evaluated in terms of hSBA GMT against 3 N. Meningitidis serogroup B reference strains at two weeks after last vaccination. | Two weeks after the second vaccination (day 45) | 
| GMRs of GMT Against 3 N. Meningitidis Serogroup B Reference Strains at Day 45. | The immunogenicity of two different lots of rMenB+OMV NZ is evaluated in terms of GMRs of GMT against 3 N. meningitidis serogroup B reference strains at two weeks after last vaccination. | Two weeks after the second vaccination (day 45) | 
| Percentage of Subjects With hSBA ≥1:5 Against Each of N. Meningitidis Serogroup B Reference Strains at Day 45. | The immune response of two different lots of rMenB+OMV NZ against each of N. Meningitidis serogroup B reference strains is evaluated in terms of percentages of subjects with hSBA ≥1:5 two weeks after the last vaccination. | Two weeks after the second vaccination (day 45) | 
| ELISA GMCs Against Vaccine Antigen 287-953 at Day 45. | The immune response of two different lots of rMenB+OMV NZ is evaluated in terms of ELISA GMCs against vaccine antigen 287-953. | Two weeks after the second vaccination (day 45) | 
| GMR of ELISA GMCs Against Antigen 287-953 at Day 45. | The immune response of two different lots of rMenB+OMV NZ against antigen 287-953 is evaluated in terms of GMRs between ELISA GMCs (day 45 vs baseline). | Two weeks after the second vaccination (day 45) | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Number of subjects reporting solicited local and systemic Adverse Events and other indicators of reactogenicity after any vaccination. | From day 1 to day 7 after any vaccination | 
| Number of Subjects Reporting Unsolicited AEs | Number of subjects reporting any Unsolicited AEs after any vaccination. | From day 1 to day 7 after any vaccination. | 
| Number of Subjects Reporting SAEs and AE Leading to Withdrawal | Number of subjects reporting any Serious AEs (SAEs), medically attended AEs and AEs that result in a subject's withdrawal from the study after any vaccination. | Throughout the study period. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Meningococcal Meningitis, prevention, vaccination, adolescents