Safety and Immunogenicity of Novartis Meningococcal B Vaccine When Administered to Immunocompromised Children and Adolescents Compared to Healthy Subjects.

Study Overview
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Brief Summary
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The study aims at evaluating the safety and immunogenicity of rMenB+OMV NZ when administered to subjects from 2 to 17 years of age with increased risk of meningococcal disease because either of primary or secondary complement deficiencies or of asplenia or splenic dysfunction. A group of healthy age-matched subjects will be enrolled to serve as a descriptive control for immunogenicity and safety.

Official Title
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A Phase IIIb, Open Label, Controlled, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of Novartis Meningococcal Group B Vaccine When Administered to Immunocompromised Patients From 2 to 17 Years of Age Who Are at Increased Risk of Meningococcal Disease Because of Complement Deficiency or Asplenia Compared to Matched Healthy Controls.

Conditions
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Meningococcal Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criterion applicable to All Groups Subjects aged 2 to 17 years (inclusive) at enrollment weighing at least 13 Kg at the time of enrollment Inclusion criterion applicable to Group A - Subjects at risk of meningococcal disease because of primary or secondary complement deficiencies Inclusion criterion applicable to Group B - Subjects at risk of meningococcal disease because of functional or anatomic asplenia Inclusion criterion applicable to Group C - healthy subjects Exclusion Criteria: Exclusion criteria applicable to All Groups (A, B and C) History of any previous immunization with a meningococcal B vaccine History of severe allergic reaction after previous vaccinations, or hypersensitivity to any component of the vaccine Known HIV infection History of any progressive or severe neurologic disorder or seizure disorder Contraindication to intramuscular injection or blood drawn Females who are pregnant, planning a pregnancy or nursing (breastfeeding) Females of childbearing potential who have not used or do not plan to use acceptable birth control measures History or any illness/condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects Exclusion criterion applicable to Groups A and B - Previous known or suspected disease caused by N. meningitidis in the last year. Exclusion criteria applicable to Group C Previous known or suspected disease caused by N. meningitidis Known or suspected impairment/alteration of the immune system

Ages Eligible for Study
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Minimum Age: 2 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Complement deficiency | Biological: rMenB+OMV<br>* 2 doses of vaccine 2 months apart<br>|
| Experimental: Group B<br>asplenia/splenic dysfunction | Biological: rMenB+OMV<br>* 2 doses of vaccine 2 months apart<br>|
| Active Comparator: Group C<br>age-matched healthy controls | Biological: rMenB+OMV<br>* 2 doses of vaccine 2 months apart<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 Using Human Complement (hSBA) Titers ≥ 5 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain. | Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 5 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+Outer Membrane Vesicle (OMV) NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine) | 
| Percentages of Subjects With hSBA Titers ≥ 8 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain. | Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 8 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine). | 
| Geometric Mean Ratios (GMRs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule. | Immunogenicity was assessed in terms of GMRs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine). | 
| Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule. | Immunogenicity was assessed in terms of GMTs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine). | 
| Percentages of Subjects With Four-fold Increases in hSBA Titers Against the Serogroup B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain. | Antibody responses were assessed in terms of percentage of subjects achieving 4-fold increase in ELISA concentrations against vaccine antigen 287-953 on Day 91 over baseline (Day 1), following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 91 (one month after the second dose of the study vaccine). | 
| Geometric Mean Concentrations (GMCs) of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule. | Immune responses were measured as Enzyme-linked Immunosorbent Assay (ELISA) GMCs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine). | 
| ELISA GMRs of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule. | Immune responses were measured as ELISA GMRs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 1 and Day 91 (one month after the second dose of the study vaccine). | 
| Percentage of Subjects With Four-fold Increases in ELISA Concentrations Against the Vaccine Antigen 287-953. | Antibody responses were assessed in terms of percentage of subjects achieving 4-fold increase in ELISA concentrations against vaccine antigen 287-953 on Day 91 over baseline (Day 1), following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61. | Day 91 (one month after the second dose of the study vaccine). | 
| Number Of Subjects With Unsolicited Adverse Events (AEs). | Safety was assessed as the number of subjects who reported unsolicited AEs collected from Day1 through Day 7 after any vaccination; serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs were collected throughout the study period (Day1-Day 91). | At Day1 through Day 7 after any vaccination and throughout the study period (Day 1 to Day 91) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Local and Systemic AEs. | Reactogenicity was presented in terms of percentages of subjects reporting solicited local and systemic AEs and other indicators. | From Day 1 until Day 7 after any vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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complement deficiency, splenic dysfunction, Meningitis, vaccination, asplenia