Study of Meninigococcal Conjugate Vaccine Containing Serogroups A,C,Y,W and X (MCV5) in Healthy Adults

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety of adjuvanted and non-adjuvanted formulations of MCV-5 vaccine. The secondary objective is to assess the immune response of adjuvanted and non-adjuvanted formulations of MCV-5 vaccine.

Detailed Description
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Prior to the study, there was no vaccine available against serogroup X of N. meningitidis. This bacterium has caused many outbreaks in Africa and Europe in recent past. It has been responsible for outbreaks between 2006 and 2010 in Kenya, Niger, Togo, Uganda, and Burkina Faso, the latter with at least 1,300 cases of serogroup X meningitis among the 6,732 reported annual cases. The WHO has expressed concerns over the lack of a serogroup X vaccine and has encouraged more research into it. As a result, Serum Institute of India Private Limited (SIIPL) has developed the candidate vaccine MCV-5 (currently renamed NmCV-5), which is a polyvalent conjugate vaccine composed of serogroups A, C, Y, W, and X of Neisseria meningitidis capsular polysaccharides, conjugated to protein carriers, CRM and tetanus toxoid, with aluminum phosphate as an adjuvant. It is intended for the prevention of meningitis and/or septicemia caused by serogroups A, C, Y, W, and X of N. meningitidis in countries where the disease is endemic and causes large epidemics, such as the countries in the African meningitis belt. The three-group design of the study will allow safety evaluation of the adjuvanted and nonadjuvanted MCV-5 formulations. Menactra® has been chosen as the control vaccine, because of the large safety database accumulated since the vaccine has been introduced in the USA in 2005 and progressively in other countries

Official Title
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A Phase 1, Double Blind, Randomized, Controlled Study to Evaluate the Safety and Immunogenicity of a New Meningococcal Conjugate Vaccine Containing Serogroups A,C,Y,W and X in Healthy Adults

Conditions
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Meningococcal Vaccines

Intervention / Treatment
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* Biological: Adjuvanted MCV-5
* Biological: Non-Adjuvanted MCV-5
* Biological: Menactra®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-45 years Written informed consent of volunteers Healthy as established by medical history, laboratory evaluation and screening evaluations Participants are able to understand and comply with planned study procedures and be available for all study visits Female subjects must be of non-childbearing potential (defined as surgically sterile or postmenopausal for more than 1 year), or if of childbearing potential must be practicing abstinence or using an effective licensed method of birth control Exclusion Criteria: Previous vaccination against Neisseria meningitidis. Known exposure to Neisseria meningitidis in the past. History of meningitis or seizures or any neurological or psychiatric disorder. Administration of any other vaccine within 30 days prior or after administration of study vaccines. Use of any investigational or non-registered drug or vaccine within 30 days prior to the administration of study vaccines or planned during the study. History of allergic disease or known hypersensitivity to any component of the three study vaccines. History of Serious Adverse Reactions following administration of Tetanus Toxoid, Diphtheria Toxoid or CRM containing vaccines. History of Guillan-Barré syndrome. Confirmed or suspected immunosuppressive or immune-deficient condition. 10. A family history of congenital or hereditary immunodeficiency. Chronic administration (defined as more than 14 days) of immune-suppressants or other immune-modifying agents within six months prior to administration of study vaccine. 12. Laboratory confirmed infection of either hepatitis B virus (HBs Ag positive on ELISA), hepatitis C virus (anti-HCV positive on ELISA as well as PCR) or human immunodeficiency virus (HIV on ELISA). Major congenital defects or serious chronic illness. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination or laboratory screening tests. Known bleeding disorders. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of study vaccines or planned administration during the vaccine period. History (within the past year) or signs of alcohol or substance abuse. Pregnancy or lactation. A Body Mass Index (BMI) equal to or above 30. Any other condition, which in the opinion of the investigator, might interfere with the study objectives, jeopardize the safety or rights of the participant or making it unlikely the participant could complete the protocol.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCV-5 with adjuvant<br>Received a single intramuscular injection of Adjuvanted MCV-5. | Biological: Adjuvanted MCV-5<br>* Contains 5 μg each of N. meningitidis A, C, Y, W, and X polysaccharides, 2.42 mg sucrose, 0.40 mg sodium citrate, 0.098 mg tris (trometamol), 7.8 to 33.4 μg tetanus toxoid, 11.7 to 50.1 μg cross reactive material of diphtheria toxin (CRM), and 125 μg Al3+adjuvant.<br>|
| Experimental: MCV-5 without adjuvant<br>Received a single intramuscular injection of Non-Adjuvanted MCV-5. | Biological: Non-Adjuvanted MCV-5<br>* Contains 5 μg each of N. meningitidis A, C, Y, W, and X polysaccharides, 2.42 mg sucrose, 0.40 mg sodium citrate, 0.098 mg tris (trometamol), 7.8 to 33.4 μg tetanus toxoid, and 11.7 to 50.1 μg cross reactive material of diphtheria toxin (CRM).<br>|
| Active Comparator: Menactra®<br>Received a single intramuscular injection of Menactra. | Biological: Menactra®<br>* Menactra® vaccine was a clear to slightly turbid solution supplied in a 0.5 mL single dose vial. Each 0.5 mL dose of vaccine was formulated in sodium phosphate buffered isotonic sodium chloride solution to contain four mcg each of meningococcal A, C, Y, and W-135 polysaccharides conjugated to approximately 48 μg of diphtheria toxoid protein carrier and residual amounts of formaldehyde of less than 2.66 μg (0.000532%), by calculation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Participants Experiencing Solicited Events | Solicited reactions (reactogenicity) were collected following vaccination through Day 7. If a solicited sign or symptom had started during the seven days post-vaccination period and continued beyond Day 7, it was still assessed as a solicited reaction. | 7 days | 
| Number and Percentage of Subjects Experiencing Unsolicited Adverse Events, by Severity | Adverse events (AE) were collected through day 28. Safety clinical laboratory evaluations were performed at Screening and at Day 8 and included: hemoglobin (HgB), white blood cells (WBC), platelet counts, alanine transaminase (ALT), albumin, total bilirubin, and creatinine. In addition, screening laboratory tests included serum HCG pregnancy tests for females of childbearing potential only, and screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection. AE severity was graded as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014, of the US National Institute of Health. | 28 days | 
| Number of Subjects Experiencing Serious Adverse Events | Serious adverse events (AE) were collected 6 months post-immunization. Safety clinical laboratory evaluations were performed at Screening and at Day 8 and included: hemoglobin (HgB), white blood cells (WBC), platelet counts, alanine transaminase (ALT), albumin, total bilirubin, and creatinine. In addition, screening laboratory tests included serum HCG pregnancy tests for females of childbearing potential only, and screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Participants With Seroconversion for Meningococcal Polysaccharide A, C, Y, W and X Specific Antibodies | Defined as a ≥4-fold increase in post-immunization rabbit complement serum bactericidal activity (rSBA) titer between baseline and 28 days post-vaccination. The rSBA assay (previously validated for serogroups A, C, Y, and W) was performed at the Vaccine Evaluation Unit at Public Health England (PHE) in Manchester, United Kingdom. | 28 days | 
| Number and Percentage of Participants With Seroprotection for Meningococcal Polysaccharide A, C, Y, W and X (Antibody Titer ≥1:8), at Baseline and After 28 Days | Seroprotection defined as a titer ≥1:8 in post-immunization rabbit complement serum bactericidal activity (rSBA) titer between baseline and 28 days post-vaccination. The rSBA assay (previously validated for serogroups A, C, Y, and W) was performed at the Vaccine Evaluation Unit at Public Health England (PHE) in Manchester, United Kingdom. | Baseline and Day 29 | 
| Number and Percentage of Participants With Seroprotection for Meningococcal Polysaccharide A, C, Y, W and X (Antibody Titer ≥1:128), at Baseline and After 28 Days | Seroprotection defined as a titer ≥1:128 in post-immunization rabbit complement serum bactericidal activity (rSBA) titer between baseline and 28 days post-vaccination. The rSBA assay (previously validated for serogroups A, C, Y, and W) was performed at the Vaccine Evaluation Unit at Public Health England (PHE) in Manchester, United Kingdom. | Baseline and Day 29 | 
| Geometric Mean Titer (GMT) of Meningococcal Polysaccharide A, C, Y, W and X Specific Antibodies at Baseline and After 28 Days | Measured with rabbit complement serum bactericidal activity (rSBA) assay at baseline and 28 days post-vaccination. The rSBA assay (previously validated for serogroups A, C, Y, and W) was performed at the Vaccine Evaluation Unit at Public Health England (PHE) in Manchester, United Kingdom. | Baseline and Day 29 | 
| Geometric Mean Fold Change in Meningococcal Polysaccharide A, C, Y, W and X Specific Antibody Titers | Measured with rabbit complement serum bactericidal activity (rSBA) assay at baseline and 28 days post-vaccination. The rSBA assay (previously validated for serogroups A, C, Y, and W) was performed at the Vaccine Evaluation Unit at Public Health England (PHE) in Manchester, United Kingdom. | 28 days |