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

• ClinicalTrials.gov Identifier: NCT02842866
• Recruitment Status: Completed
• First Posted: July 25, 2016
• Results First Posted: February 18, 2020
• Last Update Posted: June 5, 2020
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Meningitis; Meningococcal Meningitis; Meningococcal Infections	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	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 907 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adults Age 56 Years and Older
• Actual Study Start Date: July 15, 2016
• Actual Primary Completion Date: February 13, 2017
• Actual Study Completion Date: February 13, 2017

Arms and Interventions

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 Name: 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 Name: Menomune® - A/C/Y/W-135

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine [ Time Frame: Day 30 (Post-vaccination) ]
   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.

Secondary Outcome Measures :

1. Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine [ Time Frame: Day 30 (Post-vaccination) ]
   GMTs of antibodies against meningococcal serogroups A, C, Y, and W were measured by hSBA method.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Chandler, Arizona, United States, 85224

United States, California

Anaheim, California, United States, 92801

San Diego, California, United States, 92103

United States, Connecticut

Waterbury, Connecticut, United States, 06708

United States, 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

United States, Kansas

Lenexa, Kansas, United States, 66219

Newton, Kansas, United States, 67114

Wichita, Kansas, United States, 67205

United States, Maryland

Elkridge, Maryland, United States, 21075

United States, Massachusetts

Quincy, Massachusetts, United States, 02169

United States, Michigan

Troy, Michigan, United States, 48098

United States, Missouri

Saint Louis, Missouri, United States, 63141

United States, New York

Endwell, New York, United States, 13760

United States, North Carolina

Greensboro, North Carolina, United States, 27408

Raleigh, North Carolina, United States, 27612

Winston-Salem, North Carolina, United States, 27103

United States, North Dakota

Fargo, North Dakota, United States, 58104

United States, Ohio

Cincinnati, Ohio, United States, 45236

Cincinnati, Ohio, United States, 45246

United States, Oregon

Grants Pass, Oregon, United States, 97527

United States, Pennsylvania

Allentown, Pennsylvania, United States, 18012

Uniontown, Pennsylvania, United States, 15401

United States, South Carolina

Mount Pleasant, South Carolina, United States, 29464

Mount Pleasant, South Carolina, United States, 29646

United States, Texas

Dallas, Texas, United States, 75231

Dallas, Texas, United States, 75234

United States, Utah

South Jordan, Utah, United States, 84095

West Jordan, Utah, United States, 84088

United States, Virginia

Charlottesville, Virginia, United States, 22911

Puerto Rico

San Juan, Puerto Rico, 00918

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

  Study Documents (Full-Text)

Documents provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Study Protocol  [PDF] May 20, 2016

Statistical Analysis Plan  [PDF] July 7, 2016

More Information

Publications of Results:

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02842866
• Other Study ID Numbers: MET49
• First Posted: July 25, 2016
• Results First Posted: February 18, 2020
• Last Update Posted: June 5, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to participant 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. Participant 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://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Meningitis; Meningococcal Meningitis; Meningococcal Infections; MenACYW conjugate vaccine; Menomune® - A/C/Y/W-135

Additional relevant MeSH terms:

Meningococcal Infections; Meningitis, Meningococcal; Meningitis; Central Nervous System Diseases; Nervous System Diseases; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Central Nervous System Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs