Clinical trial NCT04490018: Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Compared to a Meningococcal Reference Vaccine, and When Given Alone or With Two Other Vaccines in Healthy Adolescents
Official title: Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix®, and When Administered Alone or Concomitantly With 9vHPV and Tdap-IPV Vaccines in Healthy Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Immunisation
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-07-28
Enrollment: 463
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a parallel group prevention study with 2 groups that were observer blind (only the person administering the vaccine was unblinded), and 1 group that was open-label.
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the non-inferiority of the seroprotection rate (serum bactericidal assay using human complement \[hSBA\] titer greater than or equal to \[\>=\] 1:8) to meningococcal serogroups A, C, W, and Y following the administration of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate vaccine (MenACYW Conjugate vaccine) (Group 1) compared to a single dose of Nimenrix® (Group 2).

Secondary Objective:

To describe:

* the antibody response of meningococcal serogroups A, C, W, and Y measured by hSBA, before and 1 month following meningococcal vaccination administered alone (Groups 1 and 2) or concomitantly with 9-valent human papilloma virus (9vHPV) and tetanus, diphtheria, and acellular pertussis - inactivated polio vaccine \[adsorbed, reduced antigen(s) content\] (Tdap-IPV) vaccines (Group 3).
* the antibody response of meningococcal serogroup C measured by hSBA and serum bactericidal assay using baby rabbit complement (rSBA), before vaccination and at Day 31 after vaccination with MenACYW Conjugate vaccine or Nimenrix® (Groups 1 and 2) according to MenC primed status.
* the antibody response against antigens of 9vHPV and Tdap-IPV vaccines, before and 1 month following vaccination.
* the safety profile in each group after each and any vaccination.

Detailed description: The duration of study participation for each participant was approximately 30 to 60 days, including 2 or 3 visits (1 or 2 vaccination visit) and 1 or 2 telephone calls, depending on study Group.

\* This was the first dose of 9vHPV, of the 2-dose or 3-dose series according to the local recommendations and age of the participant. These additional vaccinations for the completion of 9vHPV schedule took place outside of the objectives and scope of this study and thus were not described in this protocol.

Eligibility criteria: Inclusion Criteria:

* Aged 10 to 17 years on the day of inclusion ('10 to 17 years' means from the day of the 10th birthday to the day before the 18th birthday).
* Meningococcal serogroup C Conjugate vaccine (MenC) naïve participants or participants having received monovalent MenC priming in infancy (less than \[\<\] 2 years of age).
* Assent form had been signed and dated by the participant as per local regulation, and Informed Consent Form had been signed and dated by the parent/legally acceptable representative and by the participant if she/he turns 18 years old during the study.
* Participants and parent/legally acceptable representative were able to attend all scheduled visits and compiled with all study procedures.
* Covered by health insurance, if required by local regulations.

Exclusion Criteria:

* Participant was 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 last vaccination. To be considered of non-childbearing potential, a female must be pre-menarche.
* Previous vaccination against meningococcal disease with either the study vaccine or another vaccine (i.e., polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, W, or Y; or meningococcal B serogroup-containing vaccine), except licensed monovalent MenC vaccination received before 2 years of age.
* Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
* Receipt of any vaccine in the 4 weeks preceding any study vaccination or planned receipt of any vaccine in the 4 weeks following any study vaccination except for influenza vaccination, which might receive at least 2 weeks before study vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines.
* History of vaccination with any tetanus, diphtheria, pertussis, or inactivated polio virus vaccine within the previous 3 years.
* Previous human papilloma virus (HPV) vaccination.
* 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.
* Known history of diphtheria, tetanus, pertussis, poliomyelitis, and/or HPV infection or disease.
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study 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.
* Personal history of new or past encephalopathy, progressive or unstable neurological disorder, or unstable epilepsy.
* Verbal report of thrombocytopenia, contraindicating intramuscular vaccination.
* 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 that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion.
* Moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination or febrile illness (temperature \>= 38.0 degree Celsius \[\>= 100.4 degree Fahrenheit\]). A prospective participant should not be included in the study until the condition had 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.
* Participant at high risk for meningococcal infection during the study (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.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, W, and Y Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® Vaccine (Non-inferiority Analysis): Groups 1 and 2
timeFrame: Day 31 (post-vaccination)
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Percentage of Participants With >= 4-Fold Rise In hSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W
timeFrame: From Baseline (Day 01) to Day 31 (post-vaccination)
measure: Percentage of Participants With Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W
timeFrame: Day 31 (post-vaccination)
measure: Geometric Mean Titers (GMTs) of Antibodies Measured by hSBA Against Meningococcal Serogroup C: Meningococcal Serogroup C Conjugate Vaccine (MenC) Primed Participants in Groups 1 and 2
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Titers (GMTs) of Antibodies Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Against Meningococcal Serogroups C: Meningococcal Serogroup C Conjugate Vaccine (MenC) Primed Participants in Groups 1 and 2
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Diphtheria, Tetanus Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Polio Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Diphtheria, Tetanus Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Polio Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Concentrations Ratios (GMCRs) of Antibodies Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Concentrations Ratios (GMCRs) of Antibodies Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Percentage of Participants With Antibody Titers Above Predefined Thresholds Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Percentage of Participants With Antibody Titers Above Predefined Thresholds Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Percentage of Participants With Vaccine Seroresponse Against Pertussis Antigens
timeFrame: Day 61 (post-vaccination for Groups 1 and 2) and Day 31 (post-vaccination for Group 3)
measure: Geometric Mean Titers (GMTs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Titers (GMTs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Geometric Mean Titers Ratios (GMTRs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine in Groups 1 and 2
timeFrame: Day 31 (post-vaccination) and Day 61 (post-vaccination)
measure: Geometric Mean Titers Ratios (GMTRs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine: Group 3
timeFrame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)
measure: Percentage of Participants With Vaccine Seroconversion Against Antigens Contained in Human Papillomavirus (HPV) Vaccine
timeFrame: Day 61 (post-vaccination for Groups 1 and 2) and Day 31 (post-vaccination for Group 3)
measure: Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)
timeFrame: Within 30 minutes post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])
measure: Number of Participants Reporting Solicited Injection Site Reactions
timeFrame: Within 7 days post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])
measure: Number of Participants Reporting Solicited Systemic Reactions
timeFrame: Within 7 days post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])
measure: Number of Participants Reporting Unsolicited Adverse Events (AEs)
timeFrame: From Day 01 up to Day 31 post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])
measure: Number of Participants Reporting Serious Adverse Events (SAEs) Including Adverse Events of Special Interest (AESI)
timeFrame: From Day 01 up to the last study day (i.e., Day 61 for Groups 1 and 2 and Day 31 for Group 3)
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Investigational Site Number :3480003
city: Győr
country: Hungary
facility: Investigational Site Number :3480001
city: Miskolc
country: Hungary
facility: Investigational Site Number :3480002
city: Szigetvár
country: Hungary
facility: Investigational Site Number :3480004
city: Szombathely
country: Hungary
facility: Investigational Site Number :3480006
city: Catanzaro
country: Italy
facility: Investigational Site Number :3800006
state: Calabria
city: Milano
country: Italy
facility: Investigational Site Number :3800002
state: Lombardia
city: Foggia
country: Italy
facility: Investigational Site Number :3800005
state: Puglia
city: Palermo
country: Italy
facility: Investigational Site Number :3800004
state: Sicilia
city: Genova
country: Italy
facility: Investigational Site Number :3800001
city: Singapore
country: Singapore
facility: Investigational Site Number :7020002
city: Sevilla
country: Spain
facility: Investigational Site Number :7240001
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number :7240002
state: Barcelona [Barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number :7240005
state: Castilla Y León
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number :7240006
state: Galicia [Galicia]
city: Madrid
country: Spain
facility: Investigational Site Number :7240003
state: Madrid, Comunidad De
city: Burriana
country: Spain
facility: Investigational Site Number :7240011
state: Valenciana, Comunidad
city: Puzol
country: Spain
facility: Investigational Site Number :7240007
state: Valenciana, Comunidad
city: Valencia
country: Spain
facility: Investigational Site Number :7240008
state: Valenciana, Comunidad
city: Valencia
country: Spain
facility: Investigational Site Number :7240004
state: Valenciana, Comunidad
city: Valencia
country: Spain
facility: Investigational Site Number :7240009
state: Valenciana, Comunidad
city: Valencia
country: Spain
facility: Investigational Site Number :7240010
state: Valenciana, Comunidad
city: Valencia
country: Spain
facility: Investigational Site Number :7240012
state: Valenciana, Comunidad
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: