A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Intervention: nOPV2 (monovalent oral polio vaccine)
Intervention description: Cohort A: 150 IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1 or 2; two 10‸6 CCID50 (50% cell culture infective dose) doses separated by 28 days.
Cohort B: 972 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 10‸5 CCID50 dose of candidate 1 or 2.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Allocation of each subject to a given group will be described in a computer-generated randomization schedule. Based on this randomization code, the study vaccine will be packaged and labeled. Medication code numbers will be preprinted on the study vaccine labels and assigned as subjects qualify for the study and are randomly assigned to dosing schedule.
Enrollment: 1025.0
Sex: All
Minimum age: 6 Weeks
Maximum age: 5 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This will be a single center, age de-escalation, partly-blinded, randomized study.

      The trial will be performed with the participation of 100 healthy children age 1-5 years who
      have been vaccinated with inactivated polio vaccine (IPV) and/or oral polio vaccine (OPV) in
      their first year of life and of 648 healthy 6 week-old infants, who will be pre-vaccinated
      with bOPV-IPV before being randomized to study groups. The allocation of 18-22 week-old
      infants to groups will be performed in a randomized manner. Following completion and Data
      Safety Monitoring Board (DSMB) review of follow-up for general safety data (Serioius Adverse
      Events -SAEs-, Important Medical Events -IMEs- and severe adverse events -AEs), a DSMB
      recommendation to proceed will result in randomization of the final cohort of infants.
      Allocation of 1 to 5 year-old children to groups will be performed in a randomized manner.

      The DSMB will establish and continuously assess stopping rules for safety.
    

Eligibility criteria:

        Inclusion Criteria:

          1. For Cohort A children enrolled at 1 to 5 years of age who have previously been fully
             vaccinated according to MoH recommendations with OPV and/or IPV.

          2. For Cohort B infants enrolled at 6 weeks of age (-1, + 2 weeks) with birth weight
             >2,500 gm. To be eligible to continue into the experimental phase of the study infants
             must be vaccinated with 3 doses of bOPV and one dose of IPV prior to administration of
             the study vaccine at 18-22 weeks of age to take into account the visit windows for
             enrollment (age 6 weeks, -1 or + 2 weeks) and subsequent OPV vaccination windows (± 1
             week). The last polio vaccine must have been administered at least 4 weeks prior to
             the first dose of study vaccine. Subjects in Cohort B who do not complete the three
             routine vaccination visits will be replaced in the study, and their parents/guardians
             will be encouraged to complete the primary vaccinations series.

          3. Healthy children without obvious medical conditions like immunodeficiency diseases,
             severe congenital malformations, severe neurological diseases or any other disease
             that require high doses of corticosteroids or immunotherapies that preclude the
             subject to be in the study as established by the medical history and physical
             examination.

          4. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per
             country regulations.

        Exclusion Criteria:

          1. For all participants the presence of anyone under 10 years of age in the subject's
             household (living in the same house or apartment unit) who does not have complete "age
             appropriate" vaccination status with respect to poliovirus vaccines at the time of
             study vaccine administration. For household members younger than 18 months age
             appropriate vaccination is at least three (3) doses of IPV. For household members
             between 18 months and 10 years "age appropriate" vaccination is at least three (3)
             doses of IPV or tOPV plus one (1) booster dose of any antipolio vaccine.

          2. For all participants having a member of the subject's household (living in the same
             house or apartment unit) who is under 6 months of age at the moment of study vaccine
             administration.

          3. For all participants having a member of the subject's household (living in the same
             house or apartment unit) who has received OPV in the previous 3 months before study
             vaccine administration.

          4. For Cohort A: receipt of polio vaccines within the 3 months prior to the
             administration of the study vaccine (number of previous polio vaccine doses to be
             documented). Any other vaccine 4 weeks before study entry.

          5. For Cohort A: any participating children attending day care or pre-school during their
             participation in the study until one month after their last nOPV2 administration.

          6. For Cohort B: any receipt of polio vaccines prior to administration of the study
             vaccine other than 3 doses of bOPV and 1 dose of IPV.

          7. Any confirmed or suspected immunosuppressive or known immunodeficient condition
             including human immunodeficiency virus (HIV) infection in the potential participant or
             any member of the subject's household.

          8. Family history of congenital or hereditary immunodeficiency.

          9. Major congenital defects or serious uncontrolled chronic illness (neurologic,
             pulmonary, gastrointestinal, hepatic, renal, or endocrine).

         10. Known allergy to any component of the study vaccines or to any antibiotics, that share
             molecular composition with the nOPV2 vaccines.

         11. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections
             (of IPV).

         12. Administration of immunoglobulins and/or any blood products since birth or planned
             administration during the study period.

         13. Acute severe febrile illness at day of vaccination deemed by the Investigator to be a
             contraindication for vaccination (the child can be included at a later time if within
             age window and all inclusion criteria are met.).

         14. Subject who, in the opinion of the Investigator, is unlikely to comply with the
             protocol or is inappropriate to be included in the study for the safety or the
             benefit-risk ratio of the subject.