Meningitis, Meningococcal Meningitis, Meningococcal Infections
Conditions
Keywords
Meningitis, Meningococcal Meningitis, Meningococcal Infections, MenACYW conjugate vaccine, Menomune® - A/C/Y/W-135
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.
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.
Interventions
0.5 milliliter (mL), Intramuscular (IM), single dose on Day 0.
BIOLOGICALMeningococcal Polysaccharide Vaccine, Groups A, C, Y, and W-135 Combined
0.5 mL, Subcutaneous (SC), single dose on Day 0.
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
56 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | 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
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Day 30 (Post-vaccination) | GMTs of antibodies against meningococcal serogroups A, C, Y, and W were measured by hSBA method. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Study was conducted from 15-July-2016 to 13-February-2017 at 35 sites in the United States and Puerto Rico.
Pre-assignment details
Total 907 participants were enrolled in the study, out of which 906 were randomized. 1 participant was not randomized to either of the 2 treatment groups; this participant was not vaccinated and did not provide blood samples, therefore not counted in any analysis.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: MenACYW Conjugate Vaccine Healthy, adult participants aged ≥56 years received a single dose of MenACYW Conjugate vaccine on Day 0. | 451 |
| 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. | 455 |
| Total | 906 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Serious Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2: Menomune® Vaccine | Total | Group 1: MenACYW Conjugate Vaccine |
|---|---|---|---|
| Age, Continuous | 67.3 years STANDARD_DEVIATION 7.53 | 67.1 years STANDARD_DEVIATION 7.52 | 66.9 years STANDARD_DEVIATION 7.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 101 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 404 Participants | 793 Participants | 389 Participants |
| Sex: Female, Male Female | 261 Participants | 520 Participants | 259 Participants |
| Sex: Female, Male Male | 194 Participants | 386 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 448 | 2 / 453 |
| other Total, other adverse events | 182 / 448 | 121 / 453 |
| serious Total, serious adverse events | 15 / 448 | 15 / 453 |
Outcome results
Primary
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.
Time frame: Day 30 (Post-vaccination)
Population: Analysis was performed on per protocol analysis set which included all participants who received at least one dose of the study vaccine, had a valid post-vaccination serology result and had no protocol deviations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup A | 58.2 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup C | 77.1 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup Y | 74.4 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup W | 62.6 percentage of participants |
| Group 2: Menomune® Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup W | 44.8 percentage of participants |
| Group 2: Menomune® Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup A | 42.5 percentage of participants |
| Group 2: Menomune® Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup Y | 43.4 percentage of participants |
| Group 2: Menomune® Vaccine | Percentage of Participants With Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup C | 49.7 percentage of participants |
Comparison: Serogroup A95% CI: [9.08, 22.2]
Comparison: Serogroup C95% CI: [21.2, 33.5]
Comparison: Serogroup Y95% CI: [24.6, 37]
Comparison: Serogroup W95% CI: [11.2, 24.2]
Secondary
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.
Time frame: Day 30 (Post-vaccination)
Population: Analysis was performed on per-protocol analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup A | 55.1 titers (1/dilutions) |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup Y | 69.1 titers (1/dilutions) |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup C | 101 titers (1/dilutions) |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup W | 28.1 titers (1/dilutions) |
| Group 2: Menomune® Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup C | 24.7 titers (1/dilutions) |
| Group 2: Menomune® Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup A | 31.4 titers (1/dilutions) |
| Group 2: Menomune® Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup W | 15.5 titers (1/dilutions) |
| Group 2: Menomune® Vaccine | Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine | Serogroup Y | 21.0 titers (1/dilutions) |
Comparison: Serogroup A95% CI: [1.4, 2.2]
Comparison: Serogroup C95% CI: [3.16, 5.33]
Comparison: Serogroup Y95% CI: [2.57, 4.23]
Comparison: Serogroup W95% CI: [1.42, 2.31]