Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adults 56 Years and Older

Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adults Age 56 Years and Older

The aim of the study was to demonstrate non-inferiority of immunogenicity and evaluate the safety of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid conjugate vaccine (MenACYW conjugate vaccine) compared to a single dose of Meningococcal Polysaccharide Vaccine Serogroups A, C, Y, and W-135 Combined (Menomune® - A/C/Y/W-135) in adults 56 years of age and older in the United States.

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 those observed following the administration of a single dose of Menomune® - A/C/Y/W-135.

Secondary objective:

-To compare the serum bactericidal assay using human complement (hSBA) antibody geometric mean titers of meningococcal serogroups A, C, Y, and W following the administration of MenACYW conjugate vaccine to those observed following the administration of Menomune® - A/C/Y/W-135.

Observational objectives:

• To describe antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA at baseline (before vaccination) and 30 days after vaccination with MenACYW conjugate vaccine or Menomune® - A/C/Y/W-135 in a subset of 100 participants per treatment group.
• To describe the safety profile of MenACYW conjugate vaccine compared to that of the licensed Menomune® - A/C/Y/W-135 after a single administration.

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 Polysaccharide Vaccine, Groups A, C, Y, and W-135 Combined

Detailed Description

Participants were randomized in a 1:1 ratio to receive a single dose of MenACYW conjugate vaccine or Menomune® - A/C/Y/W-135 on Day 0 (Visit 1).

Participants underwent immunogenicity assessment at baseline (pre-vaccination) and at 30 to 44 days post-vaccination and were also evaluated for safety up to Day 180 post-vaccination.

• Study Type: Interventional
• Enrollment (Actual): 907
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
  • California
    • Anaheim, California, United States, 92801
    • San Diego, California, United States, 92103
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Clearwater, Florida, United States, 33756
    • DeLand, Florida, United States, 32720
    • Jacksonville, Florida, United States, 32205
    • Jacksonville, Florida, United States, 32216
    • Ponte Vedra, Florida, United States, 32081
    • Port Orange, Florida, United States, 32127
    • West Palm Beach, Florida, United States, 33409
  • Kansas
    • Lenexa, Kansas, United States, 66219
    • Newton, Kansas, United States, 67114
    • Wichita, Kansas, United States, 67205
  • Maryland
    • Elkridge, Maryland, United States, 21075
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
  • Michigan
    • Troy, Michigan, United States, 48098
  • Missouri
    • Saint Louis, Missouri, United States, 63141
  • New York
    • Endwell, New York, United States, 13760
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
    • Raleigh, North Carolina, United States, 27612
    • Winston-Salem, North Carolina, United States, 27103
  • North Dakota
    • Fargo, North Dakota, United States, 58104
  • Ohio
    • Cincinnati, Ohio, United States, 45236
    • Cincinnati, Ohio, United States, 45246
  • Oregon
    • Grants Pass, Oregon, United States, 97527
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18012
    • Uniontown, Pennsylvania, United States, 15401
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
    • Mount Pleasant, South Carolina, United States, 29646
  • Texas
    • Dallas, Texas, United States, 75231
    • Dallas, Texas, United States, 75234
  • Utah
    • South Jordan, Utah, United States, 84095
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Charlottesville, Virginia, United States, 22911

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥56 years on the day of inclusion.
• Informed consent form had been signed and dated.
• Attended all scheduled visits and complied with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential (were considered of non-childbearing potential, a female must be 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) preceded 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 study vaccine. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or 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 latex or any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
• Personal history of Guillain-Barré syndrome.
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within at least 10 years of the proposed study vaccination.
• Verbal report of thrombocytopenia, contraindicating IM vaccination, in the Investigator's opinion.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM 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, was at a stage where it might interfere with trial conduct or completion.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >=100.4 degree [°] Fahrenheit [F]). A prospective participant was not 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 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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MenACYW Conjugate Vaccine; Healthy, adult participants aged greater than or equal to (≥) 56 years received a single dose of MenACYW Conjugate Vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular (IM), single dose on Day 0.; Other Names: MenACYW conjugate vaccine
Active Comparator: Group 2: Menomune® Vaccine; Healthy, adult participants aged ≥56 years received a single dose of Menomune®- A/C/Y/W-135 Vaccine on Day 0.	Biological: Meningococcal Polysaccharide Vaccine, Groups A, C, Y, and W-135 Combined; 0.5 mL, Subcutaneous (SC), single dose on Day 0.; Other Names: Menomune® - A/C/Y/W-135

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine	Vaccine seroresponse for serogroups A, C, Y, and W was measured by serum bactericidal assay using human complement (hSBA). It was defined as post-vaccination hSBA titers ≥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 Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	GMTs of antibodies against meningococcal serogroups A, C, Y, and W were measured by hSBA method.	Day 30 (Post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Esteves-Jaramillo A, Koehler T, Jeanfreau R, Neveu D, Jordanov E, Singh Dhingra M. Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in >/=56-year-olds: A Phase III randomized study. Vaccine. 2020 Jun 9;38(28):4405-4411. doi: 10.1016/j.vaccine.2020.04.067. Epub 2020 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2016
• Primary Completion (Actual): February 13, 2017
• Study Completion (Actual): February 13, 2017

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 25, 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; Menomune® - A/C/Y/W-135
• 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: MET49

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