Study of a Quadrivalent Meningococcal Conjugate Vaccine in Subjects Aged 56 and Older

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered in Subjects 56 Years of Age and Older

Primary objectives:

• To describe the antibody responses to meningococcal serogroups A, C, Y, and W 135, measured by serum bactericidal assay using human complement (hSBA) and baby rabbit complement (rSBA), induced by a single dose of Meningococcal Polysaccharide (A, C, Y, and W 135) Tetanus Protein (MenACYW) Conjugate vaccine or Menomune® - A/C/Y/W 135.
• To describe the safety profile of a single dose of MenACYW Conjugate vaccine or Menomune® - A/C/Y/W 135.

Study Overview

• Status: Completed
• Conditions: Meningitis; Meningococcal Infections; Meningococcal Meningitis; Invasive Meningococcal Disease
• Intervention / Treatment: Biological: Meningococcal Polysaccharide (A, C, Y, and W 135) Tetanus Protein Conjugate Vaccine; Biological: Meningococcal Polysaccharide Vaccine, Groups A, C, Y, W 135 Combined

Detailed Description

All participants received a single dose of their assigned vaccine on Day 0. They were assessed for immunogenicity on Day 0 and Day 30, and monitored for safety throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Scottsdale, Arizona, United States, 85251
  • Colorado
    • Denver, Colorado, United States, 80239
  • Connecticut
    • Milford, Connecticut, United States, 06460
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • Missouri
    • Saint Louis, Missouri, United States, 63141
  • Ohio
    • Columbus, Ohio, United States, 43212
  • South Carolina
    • Anderson, South Carolina, United States, 29621
  • Utah
    • Murray, Utah, United States, 84123
    • Salt Lake City, Utah, United States, 84124
    • 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 56 or older on the day of inclusion.
• Informed consent form had been signed and dated.
• Able to attend 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 used an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination).
• Participation at the time of study enrollment (or 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 preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination except for influenza vaccination, which might be received at least 2 weeks before or after the study vaccines.
• Previous vaccination against meningococcal disease with either a trial vaccine or another 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.
• Known systemic hypersensitivity to latex or any of the vaccine components, or history of a severe reaction to the vaccines 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.
• Self-reported thrombocytopenia, contraindicating IM vaccination.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM 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°Fahrenheit [≥ 38.0°Celsius]). 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 3 days prior to any blood draw. Should a participant receive oral or injectable antibiotic therapy within 3 days prior to any blood draw, the Investigator would postpone the blood draw until it had been 3 days since the participant last received oral or injectable antibiotic therapy. Postponement must still be within the timeframe for blood draw indicated in the Table of Study Procedures, when possible.
• 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MenACYW Conjugate Vaccine; Adult participants aged greater than or equal to (≥) 56 years received a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y, and W 135) Tetanus Toxoid (MenACYW) Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (A, C, Y, and W 135) Tetanus Protein Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular (IM); Other Names: MenACYW Conjugate Vaccine
Active Comparator: Group 2: Menomune® A/C/Y/W 135 vaccine; Adult participants aged ≥56 years received a single dose of Meningococcal Polysaccharide Vaccine, Groups A, C, Y, and W 135 Combined (Menomune®) vaccine on Day 0.	Biological: Meningococcal Polysaccharide Vaccine, Groups A, C, Y, W 135 Combined; 0.5 mL, Subcutaneous (SC); 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 Antibody Titers ≥1:4 and ≥1:8 Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W 135 Before Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.	Day 0 (pre-vaccination)
Percentage of Participants With Antibody Titers ≥1:4 and ≥1:8 Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W 135 Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.	Day 30 (post-vaccination)
Percentage of Participants With Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W 135 Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	Vaccine seroresponse for serogroups A, C, Y, and W 135 was measured by hSBA assay method. Seroresponse was defined as post-vaccination hSBA titers ≥1:8 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)
Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W 135 Measured by hSBA Before Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.	Day 0 (pre-vaccination)
Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W 135 Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.	Day 30 (post-vaccination)
Percentage of Participants With Antibody Titers ≥1:8 and ≥1:128 Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Against Meningococcal Serogroups A, C, Y, and W 135 Before Vaccination With MenACYW Conjugate Vaccine or Menomune®	Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by rSBA assay method.	Day 0 (pre-vaccination)
Percentage of Participants With Antibody Titers ≥1:8 and ≥1:128 Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W 135 Following Vaccination With MenACYW Conjugate Vaccine or Menomune®	Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by rSBA assay method.	Day 30 (post-vaccination)
Percentage of Participants With Vaccine Seroresponse Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W 135 Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	Vaccine seroresponse for serogroups A, C, Y, and W 135 was measured by rSBA assay method. Seroresponse was defined as post-vaccination rSBA titers ≥1:8 for participants with pre-vaccination rSBA titers <1:8, or at least a 4-fold increase in rSBA titers from pre- to post-vaccination for participants with pre-vaccination rSBA titers ≥1:8.	Day 30 (post-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W 135 Measured by rSBA Before Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 antibody titers were measured by rSBA assay method.	Day 0 (pre-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W 135 Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine	GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 antibody titers were measured by rSBA assay method.	Day 30 (post-vaccination)
Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Vaccination	An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report form (CRF) in terms of symptom and/or onset post-vaccination. Unsolicited AEs includes both serious and non-serious unsolicited AEs. A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF.	Within 30 minutes after vaccination
Number of Participants With Solicited Injection Site Reactions and Systemic Reactions After Vaccination	A solicited reaction (SR) was an adverse reaction (AR) observed and reported under the conditions (symptom and onset) prelisted in the CRF. Solicited injection site reactions included: pain, erythema, and swelling. Solicited systemic reactions included: fever, headache, malaise and, myalgia.	Within 7 days after vaccination
Number of Participants With Unsolicited Adverse Events After Vaccination	An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRF in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Non-serious AE (AE excluding SAE) which was significant and prevented daily activity was considered as Grade 3 unsolicited non-serious AE.	Within 30 days after vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Kirstein J, Pina M, Pan J, Jordanov E, Dhingra MS. Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study. Hum Vaccin Immunother. 2020 Jun 2;16(6):1299-1305. doi: 10.1080/21645515.2020.1733868. Epub 2020 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2012
• Primary Completion (Actual): January 17, 2013
• Study Completion (Actual): January 17, 2013

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 26, 2012

Study Record Updates

• Last Update Posted (Actual): April 4, 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; Menactra®; 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: MET44; U1111-1127-6804 (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