Clinical trial NCT03890367: Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Compared to Two Meningococcal Reference Vaccines in European Toddlers
Official title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix® or NeisVac-C® in Healthy Toddlers 12 to 23 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Immunisation (Healthy Volunteers)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-03-26
Enrollment: 707
Sex: ALL
Minimum age (years): 12
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary Objective:

To demonstrate:

* the non-inferiority of the seroprotection rate (antibody titers greater than or equal to \[\>=\] 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate or Nimenrix® as measured by serum bactericidal assay using human complement (hSBA). If this non-inferiority was demonstrated, then
* the non-inferiority of the antibody response (geometric mean titers \[GMT\]). If this non-inferiority was demonstrated, then
* the superiority of the antibody response (GMT). If this superiority was demonstrated, then
* the superiority of the seroprotection rate.

Or to demonstrate:

* the non-inferiority of the seroprotection rate (antibody titers \>= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate or NeisVac-C® as measured by serum bactericidal assay using baby rabbit complement (rSBA). If this non-inferiority was demonstrated, then
* the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then
* the superiority of the antibody response (GMT).

Secondary Objective:

To demonstrate:

* the non-inferiority of the seroprotection rate (antibody titers \>= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate vaccine or Nimenrix® as measured by rSBA. If this non-inferiority was demonstrated, then
* the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then
* the superiority of the antibody response (GMT).

Or to demonstrate:

* the non-inferiority of the seroprotection rate (antibody titers \>= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate vaccine or NeisVac-C® as measured by hSBA. If this non-inferiority was demonstrated, then
* the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then
* the superiority of the antibody response (GMT) .

Detailed description: Study duration per participant was 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.

Safety assessment included solicited reactions within 7 days after vaccination, unsolicited adverse events up to 30 days after vaccination, serious adverse events and adverse event of special interest throughout the study.

Eligibility criteria: Inclusion criteria :

* Aged 12 to 23 months on the day of the first study visit ("12 to 23 months" means from the 12th month after birth to the day before the 24th month after birth).
* Informed consent form (ICF) had been signed and dated by the parent(s)/legally acceptable representative(s) and by an independent witness if required by local regulations.
* Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures.

Exclusion criteria:

* Participation in the 4 weeks (28 days) preceding the 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 (28 days) preceding 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 vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines.
* Receipt of immune globulins, blood or blood-derived products in the past 3 months.
* 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, W, or Y; or meningococcal B vaccine).
* 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 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 an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.
* Personal history of Guillain-Barré syndrome.
* Thrombocytopenia, as reported by the parent/ legally acceptable representative or suspected thrombocytopenia contraindicating intramuscular vaccination in the Investigator's opinion.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.
* 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 \>= 38.0 degree 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 72 hours prior to the first blood draw.
* Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

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 Serogroup C Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Superiority Analysis)
timeFrame: Day 30 (post-vaccination)
Secondary outcomes:
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA After Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis)
timeFrame: Day 30 (post-vaccination)
measure: GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Superiority Analysis)
timeFrame: Day 30 (post-vaccination)
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Investigational Site Number 2080001
city: Hvidovre
country: Denmark
facility: Investigational Site Number 2080002
city: Odense
country: Denmark
facility: Investigational Site Number 2080003
city: Espoo
country: Finland
facility: Investigational Site Number 2460006
city: Helsinki
country: Finland
facility: Investigational Site Number 2460005
city: Järvenpää
country: Finland
facility: Investigational Site Number 2460004
city: Kokkola
country: Finland
facility: Investigational Site Number 2460008
city: Oulu
country: Finland
facility: Investigational Site Number 2460007
city: Pori
country: Finland
facility: Investigational Site Number 2460003
city: Seinäjoki
country: Finland
facility: Investigational Site Number 2460010
city: Tampere
country: Finland
facility: Investigational Site Number 2460001
city: Turku
country: Finland
facility: Investigational Site Number 2460002
city: Bramsche
country: Germany
facility: Investigational Site Number 2760004
city: Bretten
country: Germany
facility: Investigational Site Number 2760019
city: Bönnigheim
country: Germany
facility: Investigational Site Number 2760015
city: Erfurt
country: Germany
facility: Investigational Site Number 2760002
city: Hamburg
country: Germany
facility: Investigational Site Number 2760017
city: Herxheim
country: Germany
facility: Investigational Site Number 2760020
city: Hürth
country: Germany
facility: Investigational Site Number 2760007
city: Itzehoe
country: Germany
facility: Investigational Site Number 2760013
city: Mannheim
country: Germany
facility: Investigational Site Number 2760011
city: Mönchengladbach
country: Germany
facility: Investigational Site Number 2760003
city: Mönchengladbach
country: Germany
facility: Investigational Site Number 2760005
city: Schwaigern
country: Germany
facility: Investigational Site Number 2760008
city: Schweigen
country: Germany
facility: Investigational Site Number 2760009
city: Schönau
country: Germany
facility: Investigational Site Number 2760006
city: Tauberbischofsheim
country: Germany
facility: Investigational Site Number 2760018
city: Tuttlingen
country: Germany
facility: Investigational Site Number 2760010
city: Wolfsburg
country: Germany
facility: Investigational Site Number 2760012
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: