Immunogenicity and Safety of a Booster Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine

Immunogenicity and Safety of a Booster Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults

The aim of the study was to describe the safety and antibody response to booster administration with Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine in participants who received their first quadrivalent meningococcal Conjugate vaccine dose in the past 4-10 years.

Primary Objective:

• To demonstrate the non-inferiority of the vaccine seroresponse of meningococcal serogroups A, C, Y, and W following the administration of a booster dose of MenACYW Conjugate vaccine compared to those observed following the administration of a booster dose of Menactra® in participants who were first vaccinated with 1 dose of a quadrivalent meningococcal vaccine 4 to 10 years before the booster dose.

Secondary Objectives:

• To evaluate the vaccine seroresponse of meningococcal serogroups A, C, Y, and W measured using human serum bactericidal assay (hSBA) in serum specimens collected 6 days after vaccination in a subset of 120 participants.
• To evaluate the antibody responses (geometric mean titers) to serogroups A, C, Y, and W measured using hSBA on Day 0 (pre-vaccination) and Day 30 after vaccination.

Observational Objectives:

• To describe the antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA assessed at Day 0, Day 6, and Day 30 days after vaccination.
• To describe the antibody responses to the meningococcal serogroups A, C, Y, and W before and 30 days after vaccination with MenACYW Conjugate vaccine or Menactra® measured by rabbit serum bactericidal assay (rSBA) in a subset of participants.
• To describe the safety profile of MenACYW Conjugate vaccine compared to that of a licensed Menactra® after booster vaccination.

Study Overview

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

Detailed Description

Healthy adolescents and adults who had received 1 dose of a quadrivalent meningococcal Conjugate vaccine 4 to 10 years previously were randomized to receive either 1 dose of MenACYW Conjugate vaccine or licensed Menactra®. All participants underwent immunogenicity assessment at baseline (pre-vaccination) and post-vaccination and were also evaluated for safety up to Day 180 post-vaccination. In addition, a subset had an additional blood sample collected at 6 days post-vaccination for immunogenicity assessment.

• Study Type: Interventional
• Enrollment (Actual): 810
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00981
    • Investigational Site Number 030
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 016
    • Dothan, Alabama, United States, 36305
      • Investigational Site Number 032
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Investigational Site Number 026
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Investigational Site Number 022
  • California
    • Downey, California, United States, 90241
      • Investigational Site Number 005
    • La Puente, California, United States, 91744
      • Investigational Site Number 014
    • San Diego, California, United States, 92108
      • Investigational Site Number 029
    • San Diego, California, United States, 92123-1881
      • Investigational Site Number 001
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Investigational Site Number 013
    • Nicholasville, Kentucky, United States, 40356
      • Investigational Site Number 027
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site Number 015
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
      • Investigational Site Number 018
  • Michigan
    • Troy, Michigan, United States, 48098
      • Investigational Site Number 010
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Investigational Site Number 008
    • Saint Louis, Missouri, United States, 63141
      • Investigational Site Number 028
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
      • Investigational Site Number 023
    • Omaha, Nebraska, United States, 68144
      • Investigational Site Number 031
  • New York
    • Rochester, New York, United States, 14609
      • Investigational Site Number 006
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Investigational Site Number 012
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Investigational Site Number 019
    • Fairfield, Ohio, United States, 45014
      • Investigational Site Number 011
    • Huber Heights, Ohio, United States, 45424
      • Investigational Site Number 025
    • Kettering, Ohio, United States, 45429
      • Investigational Site Number 021
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16508
      • Investigational Site Number 009
    • Hermitage, Pennsylvania, United States, 16148
      • Investigational Site Number 007
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Investigational Site Number 024
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Investigational Site Number 020
    • Salt Lake City, Utah, United States, 84121
      • Investigational Site Number 003
    • South Jordan, Utah, United States, 84095
      • Investigational Site Number 017

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged >= 15 years on the day of inclusion.
• Participant has documented record of having received 1 dose of a quadrivalent meningococcal conjugate vaccine 4 to 10 years prior to study vaccination.
• Participant aged 15 to < 18 years: assent form signed and dated by the participant and informed consent form (ICF) signed and dated by the parent or guardian.
• Participant aged >=18 years: ICF signed and dated by the participant.
• Participants aged 15 to < 18 years: both the participant and parent / guardian were able to attend all scheduled visits and to comply with all trial procedures.
• Participants aged >= 18 years: able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination).
• 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 before Day 30 visit except for influenza vaccination, which may be received at least 2 weeks before study investigational vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• Previous vaccination against meningococcal disease with either an investigational or approved meningococcal B 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 travelling 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 vaccine(s) used in the trial or to a vaccine containing any of the same substances.
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.
• Personal history of Guillain-Barré syndrome.
• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the Investigator's opinion.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• Moderate or severe acute illness/infection (according to the Investigator's judgment) on the day of vaccination or febrile illness (temperature >= 100.4°Fahrenheit [F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, 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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MenACYW Conjugate Vaccine; Healthy, meningococcal vaccine-primed adolescents (greater than or equal to [>=] 15 to less than [< ]18 years) or adults (>= 18 years) received a single dose of a MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular; Other Names: MenACYW Conjugate vaccine
Active Comparator: Menactra®; Healthy, meningococcal- vaccine-primed adolescents (>= 15 to < 18 years) or adults (>= 18 years) received a single dose of Menactra ® vaccine on Day 0.	Biological: Meningococcal (Groups A, C, Y and W 135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: Menactra®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroresponse to Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	The serum bactericidal assay using human complement (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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroresponse to Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine at Day 6 After Vaccination	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 6 (post-vaccination)
Geometric Mean Titers Against Meningococcal Serogroups A, C, Y, and W Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	Meningococcal antibody responses against Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)
Number of Participants With Solicited Injection Site Reactions or Systemic Reactions Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	A Solicited Reaction (SR) was an Adverse Event (AE) that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity), erythema and swelling (Grade 1: >=25 millimeter [mm] to <= 50 mm, Grade 2: >=51 to <=100 mm, Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 1: >=38.0 degree Celsius (°C) to <=38.4°C, Grade 2: >=38.5°C to <=38.9 °C, Grade 3: >= 39°C), headache, malaise, and myalgia (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity. Number of participants with any of the Grade (1, 2 or 3) and with each Grade (1, 2 and 3) solicited injection-site and systemic reactions were reported.	Within 7 days post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Anez G, Hedrick J, Simon MW, Christensen S, Jeanfreau R, Yau E, Pan J, Jordanov E, Dhingra MS. Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III randomized study. Hum Vaccin Immunother. 2020 Jun 2;16(6):1292-1298. doi: 10.1080/21645515.2020.1733867. Epub 2020 Mar 25.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2016
• Primary Completion (Actual): December 19, 2016
• Study Completion (Actual): December 19, 2016

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: April 22, 2016
• First Posted (Estimate): April 27, 2016

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal Meningitis; Meningococcal Infections; MenACYW Conjugate vaccine; Licensed Meningococcal Conjugate Vaccine (MCV4)
• 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: MET56; U1111-1161-2710 (Other Identifier: WHO); 2018-001470-18 (EudraCT Number)

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