Safety and Immunogenicity Study of Group B Meningococcal Vaccine to Prevent Meningitis.

Study Overview
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Brief Summary
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The purpose of this study is to determine if the vaccine called Group B Meningococcal 44/76 MOS NOMV 5D Vaccine is safe and free from side effects and if it will protect people from meningitis. This study will vaccinate three groups of people. In the first 2 groups, the study will be double-blinded. This means that neither the volunteer or the medical team will know which formulation of the vaccine was administered. The third group of volunteers and the medical team will know that they are receiving the higher dose of the vaccine.

Detailed Description
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Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis that can kill children and young adults very quickly. Meningococci are divided into distinct sergroups based on their polysaccharide outer capsule, which is the usual target antigen for vaccines. Serogroup A is the main cause of epidemics in Africa and in the United States, sergroups B, C and Y predominate. In the United States, no vaccine is yet available to offer protection against serogroup B which currently accounts for 32% of all meningococcal disease in the United States. This study serves as a proof of concept for our new NOMV Group B single strain monovalent vaccine model which is obtained from a genetically modified parent. If successful we plan to develop a multivalent Group B vaccine for routine use for military recruits at the beginning of basic training, for college students, particularly those who live in dormitories, and for use by travelers to countries recognized as having hyperendemic disease.

Official Title
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Phase 1 Dose Esc Study of Safety and Immun of 3 Injections, Given at 0, 6 and 24 Wks, of Grp B Meningococcal 44/76 MOS NOMV 5D Vaccine Admin to Healthy Subjs IM With and Without Adjuvant

Conditions
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Meningitis, Meningococcal, Serogroup B

Intervention / Treatment
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* Biological: 25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine
* Biological: 50ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy military or civilian males or non-pregnant, non-lactating females Age 18-45 Give informed consent and understand risk and benefit of study Understands and willing to comply with all protocol procedures and time commitment FEMALES only: surgically sterilized or received a negative pregnancy test on day of first injection AND agrees to practice adequate birth control, if necessary, for the next 7 months after first vaccination. Exclusion Criteria: Currently has or has had a history of significant organ/system disease History of allergy to any vaccine Allergy to component of vaccine such as aluminum hydroxide Presence of significant unexplained laboratory abnormality HIV sero-positive or any other immunosuppressive state Positive test for HBsAg, or hepatitis C Ongoing drug abuse/dependence Received any live vaccine, experimental products or immunosuppressive therapy in the last 28 days or inactivated vaccine in the past 14 days, or received parenteral immunoglobulin or blood products within the past 3 months Intention to leave study area for an extended period of time during the study Females: positive urine pregnancy test prior to vaccination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Single Group Assignment
Interventional Model Description: The study was conducted as a phase 1, outpatient, dose-escalating study for the Meningococcal 44/76 MOS NOMV 5D Vaccine (lot number 1119). Two dosage levels were investigated: 25 µg with and without adjuvant and 50 µg of protein without adjuvant. Each dose was given intramuscularly at 0, 6, and 24 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1) 25ug Group B Meningococcal 44/76 MOS NOMV 5D w/o adjuvant<br>Subjects received 25ug Group B Meningococcal 44/76 MOS NOMV 5D without AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks. | Biological: 25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine<br>* The study was conducted as a phase 1, outpatient, dose-escalating study for the Meningococcal 44/76 MOS NOMV 5D Vaccine (lot number 1119). 25µg with and without adjuvant were administered. Vaccinations were given intramuscularly at 0, 6, and 24 weeks.<br>|
| Experimental: 2) 25ug Group B Meningococcal 44/76 MOS NOMV 5D with adjuvant<br>Subjects received 25ug Group B Meningococcal 44/76 MOS NOMV 5D with AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks. | Biological: 25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine<br>* The study was conducted as a phase 1, outpatient, dose-escalating study for the Meningococcal 44/76 MOS NOMV 5D Vaccine (lot number 1119). 25µg with and without adjuvant were administered. Vaccinations were given intramuscularly at 0, 6, and 24 weeks.<br>|
| Experimental: 3) 50ug Group B Meningococcal 44/76 MOS NOMV 5D w/o adjuvant<br>Subjects received 50ug Group B Meningococcal 44/76 MOS NOMV 5D without AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks. | Biological: 50ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine<br>* The study was conducted as a phase 1, outpatient, dose-escalating study for the Meningococcal 44/76 MOS NOMV 5D Vaccine (lot number 1119). 50µg without adjuvant was administered. Vaccinations were given intramuscularly at 0, 6, and 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Severity Summary of Solicited and Unsolicited Adverse Events | Solicited and unsolicited summary of severity of adverse events (AEs) during the 7 day follow-up period after each vaccination | 7 day f/u period after each vaccination | 
| Safety: Adverse Event Type Summarized by Dose | Adverse events summarized by type and dose | 7 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weeks to Serconversion | Weeks to seroconversion evaluated by serum bactericidal assay. Immunogenicity was determined by assessing the number of subjects, in each cohort, who seroconverted. Seroconversion was defined as a 4-fold or greater increase in serum bactericidal antibodies against the vaccine strain. The geometric mean bactericidal titer (GMT) for each group was determined prior to vaccination and at 2 weeks after each vaccination. For each group, the GMT ratio relative to baseline and after 1, 2, or 3 vaccinations and the 95% 2-sided confidence interval was determined. A seroconversion of ≥50% of the subjects after 2 or more doses would meet the criteria for further vaccine development. | 26 weeks | 
| Percentage of Subjects With 2-fold and 4-fold Increase IgG Antibody Conversion | Percentage of subjects with ELISA 2-fold and 4-fold increase from baseline IgG antibody Conversion | 26 weeks |