Immune Lot Consistency, Immunogenicity, and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine

Immune Lot Consistency, Immunogenicity, and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults Aged 10 to 55 Years

The purpose of the study was to evaluate immune lot consistency of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine and the immune non-inferiority compared to the licensed vaccine Menactra®, and describe the safety and additional immunogenicity of these study vaccines in adolescents and adults 10 to 55 years of age in the United States (US).

Primary Objectives:

• To demonstrate the immune lot consistency of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine with respect to serum bactericidal assay using human complement (hSBA) geometric mean titers (GMTs).
• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra®.

Secondary Objective:

• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra® in the adult population (18 to 55 years old).
• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra® in the adolescent population (10 to 17 years old).
• To compare the hSBA vaccine seroresponses of meningococcal serogroups A, C, Y, and W for each of 3 lots of MenACYW Conjugate vaccine 30 days (+14 days) after vaccination.
• To compare the hSBA antibody GMTs of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine to those observed following the administration of Menactra®.

Observational Objectives:

• To describe the safety profile of MenACYW Conjugate vaccine and that of the licensed Menactra®.

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 meningococcal-vaccine naïve adolescents and adults were randomized and received a single dose of either MenACYW Conjugate vaccine from 1 of the 3 lots (Lot 1, Lot 2, or Lot 3) or Menactra®. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30 to 44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

• Study Type: Interventional
• Enrollment (Actual): 3344
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
    • Dothan, Alabama, United States, 36305
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Glendale, Arizona, United States, 85308
    • Mesa, Arizona, United States, 85213
    • Phoenix, Arizona, United States, 85018
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
    • Jonesboro, Arkansas, United States, 72401
  • California
    • Anaheim, California, United States, 92804
    • Downey, California, United States, 90241
    • Los Angeles, California, United States, 90057
    • Paramount, California, United States, 90723
    • Redding, California, United States, 96001
    • Sacramento, California, United States, 95825
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92102
    • San Diego, California, United States, 96001
    • Santa Rosa, California, United States, 95405
    • Upland, California, United States, 91786
    • West Covina, California, United States, 91790
  • Colorado
    • Littleton, Colorado, United States, 80128
  • Florida
    • DeLand, Florida, United States, 32720
    • Hialeah, Florida, United States, 33016
    • Hialeah, Florida, United States, 33012
    • Miami, Florida, United States, 33142
    • Orlando, Florida, United States, 32806
    • Saint Petersburg, Florida, United States, 33710
    • Sarasota, Florida, United States, 34239
    • South Miami, Florida, United States, 33143
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Savannah, Georgia, United States, 31406
  • Idaho
    • Meridian, Idaho, United States, 83642
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
  • Kansas
    • Lenexa, Kansas, United States, 66219
    • Newton, Kansas, United States, 67114
    • Park City, Kansas, United States, 67219
    • Wichita, Kansas, United States, 67207
    • Wichita, Kansas, United States, 67205
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Missouri
    • Bridgeton, Missouri, United States, 63044
    • Kansas City, Missouri, United States, 64114
    • Saint Louis, Missouri, United States, 63141
  • Nebraska
    • Lincoln, Nebraska, United States, 60505
    • Lincoln, Nebraska, United States, 68522
    • Omaha, Nebraska, United States, 68114
    • Omaha, Nebraska, United States, 68134
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
    • Raleigh, North Carolina, United States, 27609
    • Raleigh, North Carolina, United States, 27612
    • Salisbury, North Carolina, United States, 28144
  • North Dakota
    • Fargo, North Dakota, United States, 58104
  • Ohio
    • Cincinnati, Ohio, United States, 45246
    • Cincinnati, Ohio, United States, 45245
    • Cleveland, Ohio, United States, 44122
    • Dayton, Ohio, United States, 45414
    • Dayton, Ohio, United States, 45419
  • Oregon
    • Corvallis, Oregon, United States, 97330
    • Grants Pass, Oregon, United States, 97527
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
    • Hermitage, Pennsylvania, United States, 16148
    • McMurray, Pennsylvania, United States, 15317
    • Upper Saint Clair, Pennsylvania, United States, 15241
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • South Carolina
    • Charleston, South Carolina, United States, 29407
    • Charleston, South Carolina, United States, 29414
    • Mount Pleasant, South Carolina, United States, 29464
  • Tennessee
    • Jackson, Tennessee, United States, 38305
    • Nashville, Tennessee, United States, 37203
    • Tullahoma, Tennessee, United States, 37388
  • Texas
    • Corpus Christi, Texas, United States, 78413
    • Fort Worth, Texas, United States, 76104
    • Fort Worth, Texas, United States, 76107
    • San Antonio, Texas, United States, 78229
    • Waxahachie, Texas, United States, 75165
  • Utah
    • Draper, Utah, United States, 84020
    • Layton, Utah, United States, 84041
    • Murray, Utah, United States, 84123
    • Orem, Utah, United States, 84058
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84109
    • South Jordan, Utah, United States, 84095
    • West Jordan, Utah, United States, 84088
    • West Jordan, Utah, United States, 83642
  • Virginia
    • Burke, Virginia, United States, 22015
    • Charlottesville, Virginia, United States, 22911
    • Charlottesville, Virginia, United States, 29902
    • Midlothian, Virginia, United States, 23113
    • Richmond, Virginia, United States, 23294

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 10 to 55 years on the day of inclusion.
• Informed consent form was signed and dated by the participant (aged 18 to 55 years) or assent form was signed and dated by the participant and informed consent form was signed and dated by the parent(s) or guardian (for participants aged 10 to < 18 years).
• Participant (>= 18 years) or participant (10 to < 18 years) and parent / guardian were able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must have been 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 prior to Visit 2 except for influenza vaccination, which may be received at least 2 weeks before or after the study investigational vaccines. This exception includes 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 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, as reported by the participant or the participant's parent / guardian, 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.
• Personal history of Guillain-Barre syndrome.
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within 10 years of the proposed study vaccination.
• 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 be included in the study until the condition was 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: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MenACYW Conjugate Vaccine Lot 1; Healthy, meningococcal-vaccine naive adolescents aged 10 to 17 years (Group 1a) and adults aged 18 to 55 years (Group 1b) received a single dose of MenACYW conjugate vaccine from lot 1 on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW conjugate vaccine
Experimental: MenACYW Conjugate Vaccine Lot 2; Healthy, meningococcal-vaccine naive adolescents aged 10 to 17 years (Group 2a) and adults aged 18 to 55 years (Group 2b) received a single dose of MenACYW conjugate vaccine from lot 2 on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW conjugate vaccine
Experimental: MenACYW Conjugate Vaccine Lot 3; Healthy, meningococcal-vaccine naive adolescents aged 10 to 17 years (Group 3a) and adults aged 18 to 55 years (Group 3b) received a single dose of MenACYW conjugate vaccine from lot 3 on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW conjugate vaccine
Active Comparator: Menactra®; Healthy, meningococcal-vaccine naive adolescents aged 10 to 17 years (Group 4a) and adults aged 18 to 55 years (Group 4b) received a single dose of Menactra® 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
Geometric Mean Titers (GMTs) of Meningococcal Serogroups A, C, Y, And W Antibodies Following Vaccination With 3 Lots of MenACYW Conjugate Vaccine	Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA). Data for this outcome measure were not planned to be collected and analyzed for the Menactra® reporting group.	Day 30 (post-vaccination)
Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W 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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine in Adults	Antibody titers against meningococcal serogroups A, C, Y, and W 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. Only adults aged 18-55 years who received a single dose of Menactra® (Group 4b) or MenACYW Conjugate vaccine (Group 1b-3b) from any of the lots 1, 2 or 3, were included in this outcome measure.	Day 30 (post-vaccination)
Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine in Adolescents	Antibody titers against meningococcal serogroups A, C, Y, and W 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. Only adolescents aged 10-17 years who received a single dose of Menactra® (Group 4a) or MenACYW Conjugate vaccine (Group 1a-3a) from any of the lots 1, 2 or 3, were included in this outcome measure.	Day 30 (post-vaccination)
Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With 3 Lots of MenACYW Conjugate Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W 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)
Geometric Mean Titers (GMTs) of Meningococcal Serogroups A, C, Y, and W Antibodies Following Vaccination With MenACYW Conjugate and Menactra®	Antibody titers of meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2016
• Primary Completion (Actual): February 28, 2017
• Study Completion (Actual): February 28, 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; Licensed MCV4 vaccine
• 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: MET43; U1111-1161-3060 (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