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

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

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.

Study Overview

• Status: Completed
• Conditions: Meningococcal Vaccines
• Intervention / Treatment: Biological: Adjuvanted MCV-5; Biological: Non-Adjuvanted MCV-5; Biological: Menactra®

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Center for Vaccine Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MCV-5 with adjuvant; Received a single intramuscular injection of Adjuvanted MCV-5.	Biological: Adjuvanted MCV-5; 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.
Experimental: MCV-5 without adjuvant; Received a single intramuscular injection of Non-Adjuvanted MCV-5.	Biological: Non-Adjuvanted MCV-5; 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).
Active Comparator: Menactra®; Received a single intramuscular injection of Menactra.	Biological: Menactra®; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PATH
• Investigators: Principal Investigator: Wilbur Chen, MD,MS, University of Maryland Scool of Medicine, Baltimore

Publications and helpful links

General Publications

• Chen WH, Neuzil KM, Boyce CR, Pasetti MF, Reymann MK, Martellet L, Hosken N, LaForce FM, Dhere RM, Pisal SS, Chaudhari A, Kulkarni PS, Borrow R, Findlow H, Brown V, McDonough ML, Dally L, Alderson MR. Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine containing serogroups A, C, Y, W, and X in healthy adults: a phase 1, single-centre, double-blind, randomised, controlled study. Lancet Infect Dis. 2018 Oct;18(10):1088-1096. doi: 10.1016/S1473-3099(18)30400-6. Epub 2018 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): October 13, 2017
• Study Completion (Actual): October 13, 2017

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 21, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: VAC-046