Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers
Condition: Meningitis; Meningococcal Meningitis; Meningococcal Infections
MeSH terms: Meningococcal Infections; Meningitis, Meningococcal; Meningitis
Intervention: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine
Intervention description: 0.5 milliliter (mL), Intramuscular; 0.5 mL, Intramuscular; 0.5 mL, Intramuscular; 0.5 mL, Intramuscular
Intervention MeSH terms: Vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 918.0
Sex: All
Minimum age: 12 Months
Maximum age: 23 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Meningitis; Meningococcal Meningitis; MenACYW Conjugate vaccine; Nimenrix®; Menjugate®

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.
    

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.