Meningococcal Serogroup ACYWX Conjugate Vaccine in Comparison With MenACWY-TT Conjugate Vaccine

NCT05093829 | Completed Phase 3 Results DMC

• 2 other identifiers: EUCC-DMID-20-0024UM1AI148689
• Study Type: interventional
• Target: 1,325
• Locations: 1 country
• Sites: 1

Brief Summary

Infants aged 9 months will be randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants randomized to the 9-month age group will be further randomized in a 2:1 ratio to receive a single dose of the experimental meningococcal vaccine (NmCV-5) or a single dose of the comparator meningococcal vaccine (MenACWY-TT). Prospectively identified and consented infants randomized to the 15-month age group will return when aged 15 months and will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT.

Conditions

Meningitis

Keywords

vaccine; meningococcal; Neisseria meningitidis; conjugate meningococcal vaccine; meningococcal serogroup X

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Seroprotection for Meningitis Serogroups A, C, W and Y

  Null hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is inferior to the immune response elicited by one dose of MenACWY-TT. Alternative hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT, where "S" denotes one of the meningitis serogroups: A, C, W or Y. Endpoints are the seroprotective response at Day 29 to serogroups A, C, W and Y in the NmCV-5 arm and seroprotective response at Day 29 to serogroups A, C, W and Y in the MenACWY-TT arm with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100).

  Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days.

• Number of Participants With Seroprotection for Meningitis Serogroup X (NmCV-5) vs Lowest Comparator (MenACWY-TT)

  Null hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is inferior to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Alternative hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm and the minimum seroprotective response among serogroups A, C, W and Y in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months). Proportions and difference in proportions are reported as percentages (number of infants per 100).

  Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days.

Secondary Outcomes (11)

• Number of Participants With Serious Adverse Events (SAE)

  Measured from time of meningococcal vaccination to Study Day 181 or early study termination, whichever is earlier. Follow-up time to Study Day 181 visit was a mean (s.d.) of 180.8 (3.0) days.

• Number of Participants With Solicited Adverse Events (Reactogenicity)

  Measured from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days) for all participants.

• Number of Participants With Unsolicited Adverse Events

  Measured from time of meningococcal vaccination to Study Day 29 (28 days) for all participants.

• Number of Participants With Seroprotection for Meningitis Serogroup X

  Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days.

• Number of Participants With Seropositive Response to Measles Vaccine

  Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days.

Study Arms (4)

Vaccination at 9 months of age with NmCV-5

EXPERIMENTAL

Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 9 months of age, while receiving the current Mali EPI schedule of vaccines.

Biological: NmCV-5

Vaccination at 9 months of age with MenACWY-TT

ACTIVE COMPARATOR

Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 9 months of age, while receiving the current Mali EPI schedule of vaccines.

Biological: MenACWY-TT

Vaccination at 15 months of age with NmCV-5

EXPERIMENTAL

Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 15 months of age, while receiving the current Mali EPI schedule of vaccines.

Biological: NmCV-5

Vaccination at 15 months of age with MenACWY-TT

ACTIVE COMPARATOR

Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 15 months of age, while receiving the current Mali EPI schedule of vaccines.

Interventions

NmCV-5 BIOLOGICAL

NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT).

Vaccination at 15 months of age with NmCV-5; Vaccination at 9 months of age with NmCV-5

MenACWY-TT BIOLOGICAL

MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer.

Also known as: Nimenrix

Vaccination at 9 months of age with MenACWY-TT

Eligibility Criteria

• Age: 9 Months - 11 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male and female children between 9 months and 11 months old inclusive.
• Parent(s)/legal guardian(s) have provided written informed consent, after the nature of the study has been explained according to local regulatory requirements.
• The investigator believes that their parent(s)/guardian(s) will be available for all the subjects visits and will comply with the requirements of the protocol (e.g., timely reporting of adverse events).
• Individual is in good health as determined by medical history, physical examination, and clinical judgement of the investigator.
• Individual has completed their local infant EPI vaccines, not including 9-month EPI vaccines (at the 9-month visit) or 15- month EPI vaccines (at the 15-month visit). A birth dose of oral polio vaccine is not required.

You may not qualify if:

• History of receipt of any meningococcal vaccine.
• Has received a measles-containing vaccine.
• Current or previous, confirm 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 or study vaccination (for the 15-month age group).
• History of severe allergic reactions after previous vaccinations or hypersensitivity to any study vaccine component including tetanus, diphtheria and mutant 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 or altered function of the immune system (e.g., immunodeficiency, autoimmune conditions, malnutrition).
• Have any bleeding disorder which is considered a contraindication to intramuscular injection or blood draw.
• History of either hepatitis B or hepatitis C virus infection, human immunodeficiency virus infection, or hereditary immunodeficiency.
• Presence of major and clinically significant 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 14 days prior to enrolment in the study or planned administration of any vaccine within 14 days before or after study vaccination.
• Use of any investigational or non-registered drug or vaccine within 28 days prior to the administration of study vaccine or planned during the study.
• Malaria infection as confirmed by a Rapid Diagnostic Test. Note: subjects positive at screening may be treated for malaria as per national guidelines outside of the study, and if the subject remains eligible, vaccinated no earlier than 5 days after completing treatment.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Centre pour le Developpement des Vaccins du Mali

Bamako, Mali

Location

Related Publications (2)

• Diallo F, Haidara FC, Tapia MD, Dominguez Islas CP, Alderson MR, Hausdorff WP, Martellet L, Hosken N, Kapse D, Kulkarni PS, Townsend-Payne K, Vanni F, Posavad CM, Sow SO, Kotloff KL, Chen WH; NmCV-5 EPI study team. Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2025 Mar 29;405(10484):1069-1080. doi: 10.1016/S0140-6736(25)00046-7. Epub 2025 Mar 11.

  PMID: 40086461 DERIVED

• Stephens DS. Global Control of Meningococcal Disease. N Engl J Med. 2023 May 25;388(21):2003-2005. doi: 10.1056/NEJMe2301698. No abstract available.

  PMID: 37224203 DERIVED

MeSH Terms

Conditions

Meningitis

Interventions

NmCV-5 vaccine; tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine

Condition Hierarchy (Ancestors)

Neuroinflammatory Diseases; Nervous System Diseases

Results Point of Contact

• Title: Wilbur H. Chen, M.D., M.S., FACP, FIDSA
• Organization: University of Maryland School of Medicine

wchen@som.umaryland.edu

410-706-5328

Study Officials

• Wilbur Chen, MD, MS

  University of Maryland, Baltimore

  STUDY CHAIR

• Karen Kotloff, MD

  University of Maryland, Baltimore

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 26, 2021
• Study Start: March 24, 2022
• Primary Completion: March 10, 2023
• Study Completion: February 20, 2025
• Last Updated: March 31, 2026
• Results First Posted: May 7, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)