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

• ClinicalTrials.gov Identifier: NCT01732627
• Recruitment Status: Completed
• First Posted: November 26, 2012
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Meningitis; Meningococcal Meningitis; Meningococcal Infections; Invasive Meningococcal Disease	Biological: Meningococcal Polysaccharide (A, C, Y, and W 135) Tetanus Protein Conjugate Vaccine; Biological: Meningococcal Polysaccharide Vaccine, Groups A, C, Y, W 135 Combined	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered in Subjects 56 Years of Age and Older
• Actual Study Start Date: November 12, 2012
• Actual Primary Completion Date: January 17, 2013
• Actual Study Completion Date: January 17, 2013

Arms and Interventions

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 Name: 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 Name: Menomune® A/C/Y/W 135

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Day 0 (pre-vaccination) ]
   Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.
2. 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 [ Time Frame: Day 30 (post-vaccination) ]
   Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.
3. 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 [ Time Frame: Day 30 (post-vaccination) ]
   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.
4. 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 [ Time Frame: Day 0 (pre-vaccination) ]
   GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.
5. 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 [ Time Frame: Day 30 (post-vaccination) ]
   GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 were measured by hSBA assay method.
6. 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® [ Time Frame: Day 0 (pre-vaccination) ]
   Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by rSBA assay method.
7. 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® [ Time Frame: Day 30 (post-vaccination) ]
   Antibody titers against meningococcal serogroups A, C, Y, and W 135 were measured by rSBA assay method.
8. 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 [ Time Frame: Day 30 (post-vaccination) ]
   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.
9. 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 [ Time Frame: Day 0 (pre-vaccination) ]
   GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 antibody titers were measured by rSBA assay method.
10. 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 [ Time Frame: Day 30 (post-vaccination) ]
    GMTs of antibodies against meningococcal serogroups A, C, Y, and W 135 antibody titers were measured by rSBA assay method.
11. Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Vaccination [ Time Frame: Within 30 minutes 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.
12. Number of Participants With Solicited Injection Site Reactions and Systemic Reactions After Vaccination [ Time Frame: Within 7 days 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.
13. Number of Participants With Unsolicited Adverse Events After Vaccination [ Time Frame: Within 30 days 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.

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 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.

Contacts and Locations

Locations

United States, Arizona

Chandler, Arizona, United States, 85224

Scottsdale, Arizona, United States, 85251

United States, Colorado

Denver, Colorado, United States, 80239

United States, Connecticut

Milford, Connecticut, United States, 06460

United States, Minnesota

Edina, Minnesota, United States, 55435

United States, Missouri

Saint Louis, Missouri, United States, 63141

United States, Ohio

Columbus, Ohio, United States, 43212

United States, South Carolina

Anderson, South Carolina, United States, 29621

United States, Utah

Murray, Utah, United States, 84123

Salt Lake City, Utah, United States, 84124

West Jordan, Utah, United States, 84088

United States, Virginia

Charlottesville, Virginia, United States, 22911

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Publications of Results:

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01732627
• Other Study ID Numbers: MET44; U1111-1127-6804 ( Other Identifier: WHO )
• First Posted: November 26, 2012
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 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; Menactra®; 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