Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds

A Phase 2, Observer-blind, Randomized, Controlled Study to Evaluate the Safety and Immunogenicity of Two Formulations of Investigational Meningococcal Groups ACYWX Conjugate Vaccine, Administered to Healthy Malian Children 12-16 Months of Age

Out of the 13 identified serogroups of Neisseria meningitidis (Nm) the six serogroups (A, B, C, W, Y and X) are responsible for majority of infections. Presently available vaccines effectively protect against A, B, C, W and Y serogroups; but no vaccine that is protective against serogroup X is available yet.

Serum Institute of India Private Limited (SIIPL) has developed a conjugate vaccine against serogroups A, C, Y, W and X (NmCV-5).

The first-in-human Phase 1 study was among 60 healthy adults in USA did not show no any safety issues.

This phase 2 study is designed to evaluate safety and immunogenicity of the non-adjuvanted and adjuvanted formulations of NmCV-5 in healthy children 12-16 months of age, in comparison with the licensed quadrivalent meningococcal conjugate vaccine (Menactra®).

Both vaccines will be administered in two dose schedule 3 months apart. among vaccine-naïve healthy subjects in Mali. Safety will be assessed by collecting solicited reactions till day 7 post each dose whereas adverse events will be collected throughout the study. Each subject will be followed up for 84 days post each vaccine dose.

The vaccine immunogenicity will measured using a rabbit complement serum bactericidal activity assay (rSBA).

Study Overview

• Status: Completed
• Conditions: Meningitis, Meningococcal
• Intervention / Treatment: Biological: Adjuvanted study formulation NmCV-5; Biological: Non-adjuvanted study formulation NmCV-5; Biological: Menactra

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Phase 2

Contacts and Locations

Study Locations

• 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: 1 year to 1 year (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female children between 12 months and 16 months old inclusive (minimum 365 days of age and maximum 16 months plus 29 days of age);
• For whom parent(s)/legal guardian(s) have given written informed consent after the nature of the study has been explained according to local regulatory requirements;
• Who the investigator believes that their parent(s)/ guardian(s) will be available for all the subject visits and would comply with the requirements of the protocol (e.g., timely reporting of adverse events, availability for study site visits and home visits);
• Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
• Individuals who completed their local infant EPI schedule through 9 months of age (except MenAfriVac dose). A birth dose of OPV is not required)

Exclusion Criteria:

• History of any meningococcal vaccine administration.
• Current or previous, confirmed or suspected disease caused by N. meningitidis.
• Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrolment.
• History of severe allergic reactions after previous vaccinations or hypersensitivity to any study vaccine component including tetanus, diphtheria and diphtheria toxoid (CRM197).
• Acute or chronic, clinically significant pulmonary, cardiovascular, metabolic, neurological, hepatic, or renal functional abnormality, as determined by medical history or physical examination.
• Any confirmed or suspected condition with impaired/altered function of immune system (immunodeficient or autoimmune conditions).
• Have any bleeding disorder which is considered as a contraindication to intramuscular injection or blood draw.
• Severe acute malnutrition.
• A family history of congenital or hereditary immunodeficiency.
• History of either hepatitis B or hepatitis C virus infection or human immunodeficiency virus infection.
• Major congenital defects.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg per day. Inhaled, intranasal and topical steroids are allowed).
• Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period.
• Administration of any vaccine within 28 days prior to enrolment in the study or planned administration of any vaccine within 14 days before or after any study vaccination.
• 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.
• Malaria infection as confirmed by a Rapid Diagnostic Test.
• Individuals who are close family members of individuals conducting this study.
• Have experienced a moderate or severe acute infection and/or fever (defined as temperature ≥ 37.5°C) within 3 days prior to enrolment.
• Have received systemic antibiotic treatment within 3 days prior to enrolment.
• Non-residence in the study area or intent to move out within six months.
• Any condition which, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study

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: Adjuvanted study formulation NmCV-5; Subjects in this arm will receive adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.	Biological: Adjuvanted study formulation NmCV-5; Adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Alum as adjuvant with Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine; Other Names: Adj MenACYWX
EXPERIMENTAL: Non-adjuvanted study formulation NmCV-5; Subjects in this arm will receive non-adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.	Biological: Non-adjuvanted study formulation NmCV-5; Non-adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains 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. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.	Biological: Menactra; Menactra is available as ready to used solution containing polysacchride 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
Severe Solicited Adverse Event	Percentage of subjects with at least one severe solicited AE within 7 days after any study vaccination (Days 0-6 and Days 84-90)	7 days post each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotective rSBA Titres	Percentage of subjects with rSBA titer ≥ 8 against serogroups A, C, W, Y and X at Visits Day 0 (Baseline), Day 28 (28 days after dose 1), Day 84 (prior to dose 2) and Day 112 (28 days after dose 2)	112 days
Long Term Protective rSBA Titres	Percentage of subjects with rSBA titer ≥ 128 against serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112	112 days
Rise in rSBA Titres	Percentage of subjects with fourfold rise in rSBA titers against serogroups A, C, W, Y and X at Visits Day 28 and Day 112.; For subjects with a pre-vaccination rSBA titer < 8, a post-vaccination titer of ≥ 32;; For subjects with a pre-vaccination rSBA titer ≥ 8, an increase in rSBA titer of at least 4 times the pre-vaccination titer	112 days
Geometric Mean of rSBA Titres	rSBA GMT for serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112	112 Days
Solicited Reactions	Solicited local and systemic AEs reported during the 7 days after each vaccination (Days 0-6 and Days 84-90);	7 days post each vaccination
Adverse Events	Unsolicited AEs reported during 28 days after each vaccination (Days 0-27 and Days 84-111);	112 Days
Other Adverse Events	AEs leading to premature withdrawal during the entire study period;	168 Days
Serious Adverse Events	SAEs reported during the entire study period	168 Days

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Tapia MD, Sow SO, Naficy A, Diallo F, Haidara FC, Chaudhari A, Martellet L, Traore A, Townsend-Payne K, Borrow R, Hosken N, Smolenov I, Pisal SS, LaForce FM, Dhere RM, Kapse D, Tang Y, Alderson MR, Kulkarni PS. Meningococcal Serogroup ACWYX Conjugate Vaccine in Malian Toddlers. N Engl J Med. 2021 Jun 3;384(22):2115-2123. doi: 10.1056/NEJMoa2013615.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2017
• Primary Completion (ACTUAL): August 31, 2018
• Study Completion (ACTUAL): August 31, 2018

Study Registration Dates

• First Submitted: September 20, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (ACTUAL): September 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 10, 2021
• Last Verified: August 1, 2021

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-002; CVIA-058 (OTHER: 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