Trial to Evaluate Immunogenicity Non-Inferiority, Safety and Lot-to-Lot Consistency of Biovac OCV-S to Euvichol®-Plus

Phase I/III, Multicenter, Observer-Blinded, Randomized, Active Controlled Trial to Evaluate Immunogenicity Non-Inferiority, Safety and Lot-to-Lot Consistency of Biovac OCV-S to Euvichol®-Plus in 1 to 45 Years Old South Africans

This Phase I/III clinical trial is intended to establish the immunogenicity and safety profile of Biovac OCV-S compared to available WHO pre-qualified vaccine Euvichol®-Plus in healthy adults and children and in adult people living with HIV (PLWH). The lot-to-lot consistency of Biovac OCV-S in healthy adults will also be determined.

This is a phase I/III, multicenter, observer-blinded, age-descending, randomized, active controlled trial being conducted in South Africa to evaluate the immunogenicity non-inferiority and safety of Biovac OCV-S compared to Euvichol®-Plus among adults and children, and to evaluate the lot-to-lot consistency of Biovac OCV-S in adults.

A total of 2824 participants aged 1-45 years will be enrolled in the study in 4 cohorts: cohort A (1272 healthy adults aged 18-45 years), cohort AA (160 people living with HIV (PLWH) aged 18-45 years), cohort B (696 healthy children aged 6-17 years), and cohort C (696 healthy children aged 1-5 years). Participants in cohort A will be randomized into 4 arms to receive either one of the 3 lots of Biovac OCV-S or to receive the comparator Euvichol®-Plus in 1:1:1:1 ratio. Participants in cohorts AA, B and C will each be randomized into 2 arms to receive either Biovac OCV-S or Euvichol®-Plus in 3:1 ratio.

Each of the study participants will receive the assigned investigational product Biovac OCV-S or Euvichol®-Plus given orally in 2 doses at 2 weeks interval and will be followed up for safety and immunogenicity at specific time points. Each participant will be in the study for approximately 27 weeks.

Inclusion Criteria:

Inclusion Criteria (for healthy/HIV-negative cohorts A, B and C)

1. Healthy participants aged 1 to 45 years at consent
2. Participants/Parent(s)/Legally Authorized Representative (LAR) willing to provide informed consent/assent
3. HIV negative
4. Not pregnant or lactating

Inclusion Criteria (for PLWH (HIV-positive) cohort AA)

1. PLWH adults aged 18 to 45 years at consent
2. Participants on anti-retroviral (ARV) therapy with CD4 counts >350 and viral loads that are undetectable.
3. Not pregnant or lactating

Exclusion Criteria:

1. Known history or allergy to investigational vaccine components, other preventive vaccines, or any other allergies
2. Individuals with major congenital abnormalities
3. Known history of immune function disorders including immunodeficiency diseases (known HIV infection in healthy participant cohorts) or other immune function disorders (all cohorts).
4. Use of systemic steroids within past 6 months (>10 mg/day prednisone equivalent for periods exceeding 2 consecutive weeks), or receive chemotherapy, radiation therapy or other immunosuppressive drugs within the past 6 months.
5. Behavioral or cognitive impairment, chronic substance abuse, or psychiatric disease or neurological disorders.
6. Individuals with a known bleeding disorder.
7. Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months.
8. Individuals who have received other vaccines from 4 weeks prior to or within 4 weeks after any dose of the investigational product.
9. Individuals with active or previous Vibrio cholerae infection.
10. Individuals with receipt of a cholera vaccine in the past 5 years.