Study to Assess Immunegnicity & Safety of Pentavalent Meningococcal Vaccine (NmCV-5)

Phase 3, Observer-blind, Randomized, Active Controlled Trial to Assess the Safety of an Investigational Meningococcal Serogroups ACYWX Conjugate Vaccine (NmCV-5) and Compare Its Immunogenicity to a Licensed Meningococcal Serogroups ACYW Conjugate Vaccine (Menactra®), in Healthy Subjects 2 to 29 Years of Age

This observer-blind, randomized, active controlled trial will be conducted among 2-29 year olds in two sites (Mali and The Gambia). The objectives of the study are to assess and compare the immunogenicity and safety of NmCV-5 with that of Menactra.

A total of 1800 eligible participants (who or their parents/guardians have given written informed consent) will be randomised 2:1 (NmCV-5: Menactra) in each of the three age strata 18-29 years, 11-17 years & 2-10 years (400 NmCV-5 recipients & 200 Menactra recipients in each age strata).

Each subject will receive a single dose of study vaccine and will be followed up for 6 months post vaccination during which solicited reactions (for seven days), unsolicited AEs (28 days) and SAEs (until the end of study i.e. 168 days after vaccination) will be collected. A blood sample will be collected at baseline (pre-vaccination) and at day 28 post-vaccination for immunogenicity assessment by a Serum Bactericidal Activity assay using rabbit complement (rSBA).

Study Overview

• Status: Completed
• Conditions: Meningococcal Meningitis
• Intervention / Treatment: Biological: NmCV-5; Biological: Menactra

• Study Type: Interventional
• Enrollment (Actual): 1800
• Phase: Phase 3

Contacts and Locations

Study Locations

• Gambia
  • Fajara, Gambia
    • Medical Research Council Unit the Gambia at the London School of Hygiene & Tropical Medicine
• Mali
  • Bamako, Mali, BP251
    • Centre pour le Développement des Vaccins du Mali, ex-Institut Marchoux, Ministry of Health, BP251

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 29 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or non-pregnant female 2 through 29 years of age, inclusive, at the time of study IP administration.
2. Written informed consent obtained from subjects at least 18 years of age or from their parent/guardian for subjects less than 18 years of age with additional subject assent obtained as appropriate for participating community (i.e. subjects at least 13 years of age in Mali or at least 12 years of age in The Gambia).
3. Subject or parent/guardian with subject reside in study site area and are able and willing to adhere to all protocol visits and procedures.
4. Female subjects of childbearing potential must have practiced adequate contraception for 28 days prior to study IP administration and agree to continue adequate contraception until completion of their Day 29 visit.
5. Female subjects of childbearing potential must have a negative pregnancy test within 24 hours prior to study IP administration

Exclusion Criteria:

1. Acute illness, at the time of study IP administration (once acute illness is resolved, if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility).
2. Recorded fever (for eligibility purpose defined as a body temperature greater than 37.5°C) within 3 days prior to study IP administration (once fever/acute illness is resolved, if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility).
3. Previous immunization with a Neisseria meningitidis vaccine other than MenAfriVac® during the previous five years.
4. Current or previous, confirmed disease caused by Neisseria meningitidis.
5. Household contact with or intimate exposure to an individual with any laboratory confirmed Neisseria meningitidis infection within 90 days prior to study IP administration.
6. Known hypersensitivity to any component of the study IPs (i.e., NmCV-5 or Menactra®).
7. History of significant hypersensitivity reactions to any previous vaccine.
8. Administration of any vaccine other than study IPs within 28 days prior to study IP administration or planned administration prior to completion of the study Day 29 visit.
9. Administration of any investigational drug within 30 days prior to study IP administration or planned administration during the study period.
10. Unwilling to avoid (or their child to avoid, if the subject) the ingestion of herbal or other traditional medications during the study period.
11. Administration of immunoglobulin or any blood product within 90 days prior to study IP administration or planned administration during the study period.
12. Administration of immunosuppressants or other immune modifying agents within 90 days prior to study IP administration
13. Administration of systemic antibiotic treatment within 3 days prior to study IP administration.
14. Any history of or evidence for chronic clinically significant (as per investigator assessment) disorder or disease (including, but not limited to, immunodeficiency, autoimmunity, malnutrition, congenital abnormality, bleeding disorder, and pulmonary, cardiovascular, metabolic, neurologic, renal, or hepatic disease).
15. Any history of human immunodeficiency virus, chronic hepatitis B or chronic hepatitis C infections.
16. History of meningitis, seizures, Guillain-Barré syndrome (GBS), or other neurological disorders.
17. History of or family history of congenital or hereditary immunodeficiency.
18. Any condition that in the opinion of the investigator might compromise the safety or well-being of the subject or compromise adherence to protocol procedures or interfere with planned safety and immunogenicity assessments.
19. Pregnancy
20. Previous inclusion in the study of five immediate family members (i.e., biological father, mother, subject, and brothers and sisters may be included up to a maximum of five members from the same immediate family).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NmCV-5; Subjects in this arm will receive polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. A single dose of 0.5 mL will be administered intramuscularly.	Biological: NmCV-5; Polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysaccharide antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to C reactive material (CRM) protein. The diluent is Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine.; Other Names: MenACYWX
Active Comparator: Menactra; Subjects in this arm will licensed quadrivalent conjugated vaccine against meningococcal serogroups A,C,Y, & W viz. Menactra. A single dose of 0.5 mL will be administered intramuscularly.	Biological: Menactra; Menactra is available as ready to use solution containing polysaccharide antigens A,C,Y&WX conjugated to diphtheria toxoid. Each antigen content is 4 micrograms per 0.5 mL dose of vaccine; Other Names: MenACYW-D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroresponse	Percentage of subjects with seroresponse, measured by rabbit complement serum bactericidal activity (rSBA) against serogroups A, C, Y, W and X. [Seroresponse is defined as a post-immunization (Day 29) rSBA titer of 32 or greater if the subject's pre-immunization (Day 1) rSBA titer was < 8; or a ≥ four-fold increase over baseline at Day 29 post-immunization if the subject's pre-immunization (Day 1) rSBA titer was ≥ 8].	28 Days post vaccination
Geometric mean titres	Geometric mean titers (GMTs) measured by rSBA against serogroups A, C, Y, W and X on Day 29	28 Days post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited adverse events	Solicited AEs for 7 days following vaccination	7 days post vaccination
Unsolicited adverse events	Unsolicited AEs for 28 days following vaccination	28 days post vaccination
Serious adverse events (SAEs)	SAEs for 6 months following vaccination	6 months post vaccination
Seroprotective rSBA titres	Percentage of subjects with rSBA titer of ≥ 8 against serogroups A, C, Y, W, and X at Day 1 and Day 29	28 days post vaccination
Long term protective rSBA titres	Percentage of subjects with rSBA titer of ≥ 128 against serogroups A, C, Y, W, and X at Day 1 and Day 29	28 days post vaccination

Collaborators and Investigators

• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborators: PATH

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 20, 2019
• Primary Completion (Actual): February 23, 2020
• Study Completion (Actual): March 4, 2021

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 23, 2019
• First Posted (Actual): May 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 24, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Neisseria meningitidis; conjugate meningococcal vaccine; Meningococcal serogroup X
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis
• Other Study ID Numbers: ACYWX-03; CVIA 071 (Other Identifier: PATH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No