Clinical trial NCT02955797: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers
Official title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers 12 to 23 Months of Age.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningitis
Meningococcal Meningitis
Meningococcal Infections
Keywords: Meningitis
Meningococcal Meningitis
MenACYW Conjugate vaccine
Nimenrix®
Menjugate®
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 918
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: The purpose of the study was to evaluate the immunogenicity and describe the safety of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed Meningococcal polysaccharide groups A, C, W-135 and Y (Nimenrix®) Conjugate vaccine in toddlers 12 to 23 months of age in the European Union (EU). The toddlers were either meningococcal vaccine naïve or had received monovalent meningococcal C (MenC) vaccination during infancy to evaluate any potential impact of the meningococcal vaccine background on the immunogenicity and safety profile of the investigational product.

Primary Objectives:

* To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.
* To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in meningococcal vaccine naïve toddlers.

Secondary Objectives:

* To compare the antibody responses (geometric mean titers \[GMTs\]) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by serum bactericidal assay using human complement (hSBA) in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.
* To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in meningococcal vaccine naïve toddlers.
* To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in toddlers who received monovalent MenC vaccination during infancy.

Detailed description: Healthy toddlers were randomized depending on their meningococcal priming vaccination background (either meningococcal vaccine naïve or primed with MenC) and received a single dose of either MenACYW Conjugate vaccine or Nimenrix®. They were assessed for immunogenicity at baseline (pre-vaccination) and 30 to 44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

Eligibility criteria: Inclusion Criteria:

* Aged 12 to 23 months on the day of the first study visit.
* Participants had received all recommended standard-of-care non-meningococcal vaccinations according to his/her age as per local regulations.
* Informed consent form (ICF) had been signed and dated by the parent/legally acceptable representative.
* Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures.
* Covered by health insurance if required by local regulations.
* Participants had received any meningococcal vaccine in the second year of life (i.e., from 12 months of age).
* For Inclusion in Groups 1 and 2: Participants must not had received any vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).
* For Inclusion in Groups 3 and 4: Participants must had previously received at least 1 dose of licensed monovalent meningococcal C Conjugate (MenC) vaccine during infancy (i.e., before 12 months of age).

Exclusion Criteria:

* 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 investigational 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.
* For Groups 1 and 2 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).
* For Groups 3 and 4 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent B meningococcal vaccine), except licensed monovalent meningococcal C Conjugate (MenC) vaccination received during infancy.
* 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 trial 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.
* Verbal report of thrombocytopenia, as reported by the parent/legally acceptable representative 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, 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 a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

Primary outcomes:
measure: Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy
timeFrame: Day 30 (post-vaccination)
measure: Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Meningococcal Vaccine Naïve Toddlers
timeFrame: Day 30 (post-vaccination)
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy
timeFrame: Day 30 (post-vaccination)
measure: Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Vaccine Naive Toddlers
timeFrame: Day 30 (post-vaccination)
measure: Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Toddlers Who Had Received Monovalent MenC Vaccination During Infancy
timeFrame: Day 30 (post-vaccination)
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: Investigational Site 309
city: Helsinki
country: Finland
facility: Investigational Site 301
city: Helsinki
country: Finland
facility: Investigational Site 306
city: Järvenpää
country: Finland
facility: Investigational Site 302
city: Kokkola
country: Finland
facility: Investigational Site 304
city: Oulu
country: Finland
facility: Investigational Site 307
city: Pori
country: Finland
facility: Investigational Site 303
city: Seinäjoki
country: Finland
facility: Investigational Site 305
city: Tampere
country: Finland
facility: Investigational Site 308
city: Turku
country: Finland
facility: Investigational Site 310
city: Aschaffenburg
country: Germany
facility: Investigator Site 412
city: Bramsche
country: Germany
facility: Investigator Site 401
city: Bretten
country: Germany
facility: Investigator Site 407
city: Bönnigheim
country: Germany
facility: Investigator Site 411
city: Datteln
country: Germany
facility: Investigator Site 413
city: Goch
country: Germany
facility: Investigator Site 408
city: Hamburg
country: Germany
facility: Investigator Site 406
city: Hamburg
country: Germany
facility: Investigator Site 415
city: Ludwigsfelde
country: Germany
facility: Investigator Site 404
city: Rosenheim
country: Germany
facility: Investigator Site 409
city: Tauberbischofsheim
country: Germany
facility: Investigator Site 402
city: Tauberbischofsheim
country: Germany
facility: Investigator Site 403
city: Budapest
country: Hungary
facility: Investigational Site 102
city: Budapest
country: Hungary
facility: Investigational Site 101
city: Győr
country: Hungary
facility: Investigational Site 104
city: Miskolc
country: Hungary
facility: Investigational Site 105
city: Szeged
country: Hungary
facility: Investigational Site 103
city: Székesfehérvár
country: Hungary
facility: Investigational Site 106
city: Barcelona
country: Spain
facility: Investigator Site 203
city: Galicia
country: Spain
facility: Investigator Site 204
city: Madrid
country: Spain
facility: Investigator Site 205
city: Madrid
country: Spain
facility: Investigator Site 202
city: Sevilla
country: Spain
facility: Investigator Site 201
Study officials:
affiliation: Sanofi Pasteur SA
name: Medical Director
role: STUDY_DIRECTOR
References: