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

Phase 1

Completed

Conditions: Meningococcal Vaccines

Interventions: Biological: Menactra®
Biological: Adjuvanted MCV-5
Biological: Non-Adjuvanted MCV-5

Registration Number: NCT02810340

Lead Sponsor: PATH

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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.
1. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Menactra®	Menactra®	Received a single intramuscular injection of Menactra.
MCV-5 with adjuvant	Adjuvanted MCV-5	Received a single intramuscular injection of Adjuvanted MCV-5.
MCV-5 without adjuvant	Non-Adjuvanted MCV-5	Received a single intramuscular injection of Non-Adjuvanted MCV-5.

Primary Outcome Measures

Name	Time	Method
Number and Percentage of Participants Experiencing Solicited Events	7 days	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.
Number of Subjects Experiencing Serious Adverse Events	180 days	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.
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events, by Severity	28 days	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.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Fold Change in Meningococcal Polysaccharide A, C, Y, W and X Specific Antibody Titers	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.
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	Baseline and Day 29	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.
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	Baseline and Day 29	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.
Geometric Mean Titer (GMT) of Meningococcal Polysaccharide A, C, Y, W and X Specific Antibodies at Baseline and After 28 Days	Baseline and Day 29	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.
Number and Percentage of Participants With Seroconversion for Meningococcal Polysaccharide A, C, Y, W and X Specific Antibodies	28 days	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.