Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds
Condition: Meningitis, Meningococcal
MeSH terms: Meningitis, Meningococcal; Meningitis
Intervention: Non-adjuvanted study formulation NmCV-5; Adjuvanted study formulation NmCV-5; Menactra
Intervention description: Non-adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine.; Adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Alum as adjuvant with Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine; Menactra is available as ready to used solution containing polysacchride antigens A,C,Y&WX conjugated to diphtheria toxoid. Each antigen content is 4 micrograms per 0.5 mL dose of vaccine.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Observer blind wherein the pharmacist and other study staff involved in vaccine administration will be aware of the treatment allocation.
The other study staff involved in safety assessments will be masked to treatment arm. The laboratory involved in immunogenicity analysis will also be blinded to the treatment allocation.
Enrollment: 375.0
Sex: All
Minimum age: 12 Months
Maximum age: 16 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Neisseria meningitidis; conjugate meningococcal vaccine; meningococcal serogroup X

Summary:

      Out of the 13 identified serogroups of Neisseria meningitidis (Nm) the six serogroups (A, B,
      C, W, Y and X) are responsible for majority of infections. Presently available vaccines
      effectively protect against A, B, C, W and Y serogroups; but no vaccine that is protective
      against serogroup X is available yet.

      Serum Institute of India Private Limited (SIIPL) has developed a conjugate vaccine against
      serogroups A, C, Y, W and X (NmCV-5).

      The first-in-human Phase 1 study was among 60 healthy adults in USA did not show no any
      safety issues.

      This phase 2 study is designed to evaluate safety and immunogenicity of the non-adjuvanted
      and adjuvanted formulations of NmCV-5 in healthy children 12-16 months of age, in comparison
      with the licensed quadrivalent meningococcal conjugate vaccine (Menactra®).

      Both vaccines will be administered in two dose schedule 3 months apart. among vaccine-naïve
      healthy subjects in Mali. Safety will be assessed by collecting solicited reactions till day
      7 post each dose whereas adverse events will be collected throughout the study. Each subject
      will be followed up for 84 days post each vaccine dose.

      The vaccine immunogenicity will measured using a rabbit complement serum bactericidal
      activity assay (rSBA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female children between 12 months and 16 months old inclusive (minimum 365
             days of age and maximum 16 months plus 29 days of age);

          -  For whom parent(s)/legal guardian(s) have given written informed consent after the
             nature of the study has been explained according to local regulatory requirements;

          -  Who the investigator believes that their parent(s)/ guardian(s) will be available for
             all the subject visits and would comply with the requirements of the protocol (e.g.,
             timely reporting of adverse events, availability for study site visits and home
             visits);

          -  Individuals in good health as determined by the outcome of medical history, physical
             examination and clinical judgment of the investigator.

          -  Individuals who completed their local infant EPI schedule through 9 months of age
             (except MenAfriVac dose). A birth dose of OPV is not required)

        Exclusion Criteria:

          -  History of any meningococcal vaccine administration.

          -  Current or previous, confirmed or suspected disease caused by N. meningitidis.

          -  Household contact with and/or intimate exposure to an individual with any laboratory
             confirmed N. meningitidis infection within 60 days of enrolment.

          -  History of severe allergic reactions after previous vaccinations or hypersensitivity
             to any study vaccine component including tetanus, diphtheria and diphtheria toxoid
             (CRM197).

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, metabolic,
             neurological, hepatic, or renal functional abnormality, as determined by medical
             history or physical examination.

          -  Any confirmed or suspected condition with impaired/altered function of immune system
             (immunodeficient or autoimmune conditions).

          -  Have any bleeding disorder which is considered as a contraindication to intramuscular
             injection or blood draw.

          -  Severe acute malnutrition.

          -  A family history of congenital or hereditary immunodeficiency.

          -  History of either hepatitis B or hepatitis C virus infection or human immunodeficiency
             virus infection.

          -  Major congenital defects.

          -  Chronic administration (defined as more than 14 days) of immunosuppressants or other
             immune-modifying drugs within three months prior to the study vaccination or planned
             use throughout the study period. (For corticosteroids, this means prednisone, or
             equivalent, ≥ 0.5 mg/kg per day. Inhaled, intranasal and topical steroids are
             allowed).

          -  Administration of blood, blood products and/or plasma derivatives or any parenteral
             immunoglobulin preparation in the past 3 months or planned use throughout the study
             period.

          -  Administration of any vaccine within 28 days prior to enrolment in the study or
             planned administration of any vaccine within 14 days before or after any study
             vaccination.

          -  Use of any investigational or non-registered drug or vaccine within 30 days prior to
             the administration of study vaccines or planned during the study.

          -  Malaria infection as confirmed by a Rapid Diagnostic Test.

          -  Individuals who are close family members of individuals conducting this study.

          -  Have experienced a moderate or severe acute infection and/or fever (defined as
             temperature ≥ 37.5°C) within 3 days prior to enrolment.

          -  Have received systemic antibiotic treatment within 3 days prior to enrolment.

          -  Non-residence in the study area or intent to move out within six months.

          -  Any condition which, in the opinion of the investigator, might pose additional risk to
             the subject due to participation in the study