Healthy Volunteers (Meningococcal Infection)
Conditions
Brief summary
The primary objectives of this study are: * To describe the antibody response to meningococcal serogroups A, C, W, and Y measured by serum bactericidal assay using baby rabbit complement (rSBA) before and after a single dose of MenACYW conjugate vaccine * To describe the antibody response to meningococcal serogroups A, C, W, and Y measured by serum bactericidal assay using human complement (hSBA) before and after a single dose of MenACYW conjugate vaccine * To describe the antibody responses against tetanus toxoid at baseline and after a single dose of MenACYW conjugate vaccine * To describe the safety profile of a single dose of MenACYW conjugate vaccine
Detailed description
Study duration per participant is approximately 30 days including: 1 day of screening and vaccination, a phone call and a safety follow up/end of study visit at Day 8 and Day 30 after vaccine administration, respectively.
Interventions
Pharmaceutical form: Solution for injection Route of administration: Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
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 has been signed and dated * Able to attend all scheduled visits and to comply with all trial procedures * Intending to go on a Hajj or Umrah pilgrimage (but not within the next 10 to 12 months after vaccination)
Exclusion criteria
* Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile). * 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 study vaccine. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. * Any 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, B, C, W, or Y). * 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). * Known systemic hypersensitivity to any of the vaccine components, or history of a lifethreatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances . * Personal history of Guillain-Barre syndrome (GBS). * 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 thrombocytopenia, contraindicating intramuscular vaccination, in the Investigator's opinion. * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular 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 (eg, human immunodeficiency virus \[HIV\], hepatitis B, hepatitis C) that, in the opinion of the Investigator, is 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 ≥ 38.0 C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has 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. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y | Day 30 post-dose | Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the rSBA. Seroprotection rate is defined as percentage of participants with rSBA titer \>=1.8 who received MenACYW conjugate vaccine. Percentages are rounded off to the tenth decimal place. |
| Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA | Day 30 post-dose | Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the rSBA and the results were expressed as geometric mean titers. |
| Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA) | Day 30 post-dose | Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the hSBA and the results were expressed as geometric mean titers. |
| Geometric Mean Concentrations (GMCs) of Antibodies Against Tetanus Toxoid | Pre-dose Day 0 and Day 30 post-dose | Tetanus toxoid was contained in the investigational vaccine as a carrier protein. Anti-tetanus antibodies were measured by electrochemiluminescent (ECL) assay. The captured antibodies were then detected using a sulfotag-conjugated anti-human immunoglobulin (Ig)G conjugate. |
| Percentage of Participants Who Achieved Seroprotective Levels | Pre-dose Day 0 and Day 30 post-dose | Seroprotective levels defined as antibody titers \>= 0.01 IU/mL and \>= 0.1 IU/mL of antibody concentrations to tetanus toxoid. Tetanus toxoid was contained in the investigational vaccine as a carrier protein. Anti-tetanus antibodies were measured by ECL assay. The captured antibodies were then detected using a sulfotag-conjugated anti-human IgG conjugate. Percentages are rounded off to the tenth decimal place. |
| Number of Participants With Unsolicited Systemic Adverse Events (AEs) | Within 30 minutes post-dose | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions \[i.e.pre-listed in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination\]. |
| Number of Participants With Solicited Injection Site Reactions and Systemic Reactions | Up to 7 days post-dose | All noxious and unintended responses to a study vaccine related to any dose was considered adverse reactions (AR). A solicited reaction is an expected AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB. An injection site reaction is an AR at and around the injection site. Injection site reactions are commonly inflammatory reactions. They were considered to be related to the study vaccine administered. Systemic reactions were all ARs that were not injection or administration site reactions and included systemic manifestations such as headache, fever, as well as localized or topical manifestations that are not associated with the vaccination or administration site. |
| Number of Participants With Unsolicited Non-Serious Adverse Events | Up to Day 30 post-dose | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions (i.e. pre-listed in the CRB in terms of diagnosis and/or onset window post-vaccination). |
| Number of Participants With Serious Adverse Events (SAEs) | From Day 0 up to end of study, approximately 44 days | A SAEs is defined as any untoward medical occurrence, at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other important medical event. |
Countries
Lebanon, Turkey (Türkiye)
Participant flow
Recruitment details
The study was conducted at 3 centers in 2 countries between 08 April 2019 to 18 March 2022.
Pre-assignment details
A total of 290 participants who met all the inclusion criteria were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| MenACYW Conjugate Vaccine Participants received a single dose of meningococcal polysaccharide \[Serogroups A, C, W and Y (MenACYW conjugate vaccine)\] 0.5 mL IM injection on Day 0. | 290 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | MenACYW Conjugate Vaccine |
|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 6.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 290 Participants |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 288 |
| other Total, other adverse events | 69 / 288 |
| serious Total, serious adverse events | 6 / 288 |
Outcome results
Primary
Geometric Mean Concentrations (GMCs) of Antibodies Against Tetanus Toxoid
Tetanus toxoid was contained in the investigational vaccine as a carrier protein. Anti-tetanus antibodies were measured by electrochemiluminescent (ECL) assay. The captured antibodies were then detected using a sulfotag-conjugated anti-human immunoglobulin (Ig)G conjugate.
Time frame: Pre-dose Day 0 and Day 30 post-dose
Population: The FAS consisted of participants who received at least 1 dose of the study vaccine and had a valid post-vaccination serology result. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of Antibodies Against Tetanus Toxoid | Day 0 (pre-dose) | 0.040 International units/milliliter (IU/mL) |
| MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of Antibodies Against Tetanus Toxoid | Day 30 (post-dose) | 0.429 International units/milliliter (IU/mL) |
Primary
Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA
Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the rSBA and the results were expressed as geometric mean titers.
Time frame: Day 30 post-dose
Population: The FAS consisted of participants who received at least 1 dose of the study vaccine and had a valid post-vaccination serology result. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA | Serogroup A | 635 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA | Serogroup C | 2038 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA | Serogroup W | 2710 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by rSBA | Serogroup Y | 2539 Titer |
Primary
Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA)
Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the hSBA and the results were expressed as geometric mean titers.
Time frame: Day 30 post-dose
Population: The FAS consisted of participants who received at least 1 dose of the study vaccine and had a valid post-vaccination serology result. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA) | Serogroup A | 31.9 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA) | Serogroup C | 135 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA) | Serogroup W | 56.3 Titer |
| MenACYW Conjugate Vaccine | Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y Measured by Serum Bactericidal Assay Using Human Complement (hSBA) | Serogroup Y | 130 Titer |
Primary
Number of Participants With Serious Adverse Events (SAEs)
A SAEs is defined as any untoward medical occurrence, at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
Time frame: From Day 0 up to end of study, approximately 44 days
Population: The SafAS consisted of participants who had received at least 1 dose of the study vaccine and had any safety data available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MenACYW Conjugate Vaccine | Number of Participants With Serious Adverse Events (SAEs) | 6 Participants |
Primary
Number of Participants With Solicited Injection Site Reactions and Systemic Reactions
All noxious and unintended responses to a study vaccine related to any dose was considered adverse reactions (AR). A solicited reaction is an expected AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB. An injection site reaction is an AR at and around the injection site. Injection site reactions are commonly inflammatory reactions. They were considered to be related to the study vaccine administered. Systemic reactions were all ARs that were not injection or administration site reactions and included systemic manifestations such as headache, fever, as well as localized or topical manifestations that are not associated with the vaccination or administration site.
Time frame: Up to 7 days post-dose
Population: The SafAS consisted of participants who had received at least 1 dose of the study vaccine and had any safety data available. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Number of Participants With Solicited Injection Site Reactions and Systemic Reactions | Solicited injection site reaction | 39 Participants |
| MenACYW Conjugate Vaccine | Number of Participants With Solicited Injection Site Reactions and Systemic Reactions | Solicited systemic reaction | 59 Participants |
Primary
Number of Participants With Unsolicited Non-Serious Adverse Events
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions (i.e. pre-listed in the CRB in terms of diagnosis and/or onset window post-vaccination).
Time frame: Up to Day 30 post-dose
Population: The SafAS consisted of participants who had received at least 1 dose of the study vaccine and had any safety data available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MenACYW Conjugate Vaccine | Number of Participants With Unsolicited Non-Serious Adverse Events | 41 Participants |
Primary
Number of Participants With Unsolicited Systemic Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions \[i.e.pre-listed in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination\].
Time frame: Within 30 minutes post-dose
Population: The Safety analysis set (SafAS) consisted of participants who had received at least 1 dose of the study vaccine and had any safety data available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MenACYW Conjugate Vaccine | Number of Participants With Unsolicited Systemic Adverse Events (AEs) | 0 Participants |
Primary
Percentage of Participants Who Achieved Seroprotective Levels
Seroprotective levels defined as antibody titers \>= 0.01 IU/mL and \>= 0.1 IU/mL of antibody concentrations to tetanus toxoid. Tetanus toxoid was contained in the investigational vaccine as a carrier protein. Anti-tetanus antibodies were measured by ECL assay. The captured antibodies were then detected using a sulfotag-conjugated anti-human IgG conjugate. Percentages are rounded off to the tenth decimal place.
Time frame: Pre-dose Day 0 and Day 30 post-dose
Population: The FAS consisted of participants who received at least 1 dose of the study vaccine and had a valid post-vaccination serology result. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Percentage of Participants Who Achieved Seroprotective Levels | Day 0 (pre-dose): >=0.01 IU/mL | 87.8 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants Who Achieved Seroprotective Levels | Day 0 (pre-dose): >=0.1 IU/mL | 28.3 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants Who Achieved Seroprotective Levels | Day 30 (post-dose): >=0.01 IU/mL | 93.0 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants Who Achieved Seroprotective Levels | Day 30 (post-dose): >=0.1 IU/mL | 56.8 percentage of participants |
Primary
Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y
Functional meningococcal antibody activity against serogroups A, C, W, and Y were measured in a serum bactericidal assay utilizing the rSBA. Seroprotection rate is defined as percentage of participants with rSBA titer \>=1.8 who received MenACYW conjugate vaccine. Percentages are rounded off to the tenth decimal place.
Time frame: Day 30 post-dose
Population: The Full analysis set (FAS) consisted of participants who received at least 1 dose of the study vaccine and had a valid post-vaccination serology result. Only those participants with data collected are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACYW Conjugate Vaccine | Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y | Serogroup A | 90.1 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y | Serogroup C | 94.1 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y | Serogroup W | 91.3 percentage of participants |
| MenACYW Conjugate Vaccine | Percentage of Participants With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, W, and Y | Serogroup Y | 95.5 percentage of participants |