Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Children Aged 2 to 9 Years

Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Healthy Children 2 to 9 Years of Age

The purpose of the study was to evaluate the immunogenicity and describe the safety of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 (MENVEO®) vaccine in children 2 to 9 years of age in the United States (US) and Puerto Rico.

Primary objective:

- To demonstrate the non-inferiority of the vaccine seroresponse to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine compared to that observed following the administration of a single dose of MENVEO® in children aged 2 to 9 years.

Secondary objectives:

• To compare the serum bactericidal assay using human complement (hSBA) antibody geometric mean titers (GMTs) of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine to those observed following the administration of MENVEO® in children 2 to 9 years of age.
• To evaluate the hSBA antibody GMTs of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine and those observed following the administration of MENVEO® in children 2 to 5 years of age, and in children 6 to 9 years of age, respectively.
• To evaluate the hSBA vaccine seroresponse to meningococcal serogroups A, C, Y, and W before and 30 days (+14 days) post-vaccination in children 2 to 5 years of age, and in children 6 to 9 years of age, respectively.

Observational objective:

- To describe the safety profile of MenACYW Conjugate vaccine and that of the licensed MENVEO®.

Study Overview

• Status: Completed
• Conditions: Meningitis; Meningococcal Infections; Meningococcal Meningitis
• Intervention / Treatment: Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate; Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine

Detailed Description

Healthy children were randomized and received a single dose of either MenACYW Conjugate vaccine or MENVEO®. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30-44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site
    • Dothan, Alabama, United States, 36305
      • Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Investigational Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Investigational Site
  • California
    • Anaheim, California, United States, 92804
      • Investigational Site
    • Downey, California, United States, 90241
      • Investigational Site
    • Paramount, California, United States, 90723
      • Investigational Site
    • San Diego, California, United States, 92103
      • Investigational Site
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Investigational Site
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Investigational Site
    • Nicholasville, Kentucky, United States, 40356
      • Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
      • Investigational Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Investigational Site
    • Kansas City, Missouri, United States, 64114
      • Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Investigational Site
    • Cleveland, Ohio, United States, 44121
      • Investigational Site
    • Dayton, Ohio, United States, 45414
      • Investigational Site
    • Fairfield, Ohio, United States, 45014
      • Investigational Site
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Investigational Site
    • Gresham, Oregon, United States, 92103
      • Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • Investigational Site
    • Hermitage, Pennsylvania, United States, 16148
      • Investigational Site
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Investigational Site
    • Tullahoma, Tennessee, United States, 37388
      • Investigational Site
  • Utah
    • Layton, Utah, United States, 84041
      • Investigational Site
    • Orem, Utah, United States, 84057
      • Investigational Site
    • Roy, Utah, United States, 84067
      • Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • Investigational Site
    • Salt Lake City, Utah, United States, 84109
      • Investigational Site
    • South Jordan, Utah, United States, 84095
      • Investigational Site
    • Syracuse, Utah, United States, 84075
      • Investigational Site
    • West Jordan, Utah, United States, 848088
      • Investigational Site
  • Virginia
    • Midlothian, Virginia, United States, 23113
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 9 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 2 to 9 years on the day of inclusion.
• Assent form had been signed and dated by the participant (as required by local regulations) and informed consent form had been signed and dated by parent(s) or guardian.
• Participant and parent/guardian were able to attend all scheduled visits and complied with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche.
• Participation in the 4 weeks preceding the trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which might be received at least 2 weeks before or after the study investigational vaccines. This exception included monovalent, multivalent, live, and attenuated influenza vaccines.
• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (ie., mono- or polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, Y, W; or meningococcal B serogroup containing vaccine).
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.
• At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination by the Investigator's judgment.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.
• Personal history of Guillain-Barré syndrome.
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
• Moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination or febrile illness (temperature ≥100.4°F). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw.
• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

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: Group 1: MenACYW Conjugate Vaccine; Healthy, meningococcal-vaccine naïve participants aged 2 to 9 years received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate; 0.5 milliliter (mL), Intramuscular; Other Names: MenACYW Conjugate vaccine
Active Comparator: Group 2: MENVEO® Vaccine; Healthy, meningococcal-vaccine naïve participants aged 2 to 9 years received a single dose of MENVEO® Conjugate vaccine on Day 0.	Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MENVEO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse against serogroups A, C, Y, and W was defined as post-vaccination hSBA titers greater than or equal to (>=) 1:16 for participants with pre-vaccination hSBA titers less than (<) 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8.	Day 30 (post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 9 Years of Age	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 5 Years of Age	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA.	Day 30 (post-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 6 to 9 Years of Age	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA.	Day 30 (post-vaccination)
Percentage of Participants Achieving Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 5 Years of Age	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination hSBA titers <1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8.	Day 30 (post-vaccination)
Percentage of Participants Achieving Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 6 to 9 Years Age	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination hSBA titers <1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8.	Day 30 (post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Medical Officer, MD, Sanofi Pasteur Inc.

Publications and helpful links

General Publications

• Baccarini CI, Simon MW, Brandon D, Christensen S, Jordanov E, Dhingra MS. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine in Healthy Meningococcal-Naive Children 2-9 Years of Age: A Phase III, Randomized Study. Pediatr Infect Dis J. 2020 Oct;39(10):955-960. doi: 10.1097/INF.0000000000002832.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2017
• Primary Completion (Actual): October 10, 2017
• Study Completion (Actual): October 10, 2017

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal Meningitis; MenACYW Conjugate vaccine; MENVEO®
• 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; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MET35; U1111 1161 2625 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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