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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Biological Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine)
  Two doses (1.5mL) at two weeks interval given orally.
• Biological Active Comparator, Euvichol®-Plus
  Two doses (1.5mL) at two weeks interval given orally.

Primary outcome measures

• Seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa [Time frame: 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus]
• Incidence of Treatment-Emergent Adverse Events in the HIV negative group [Time frame: Within 14 days after each vaccination]

Secondary outcome measures (4)

• Geometric Mean Titer (GMT) of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa for all ages [Time frame: 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus]
• Proportion of participants showing seroconversion against Vibrio cholerae O1 Inaba and Ogawa [Time frame: 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus]
• GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in each age stratum [Time frame: 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus]
• GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in adults [Time frame: 2 weeks after second dose of 3 lots of Biovac OCV-S]

Eligibility criteria

Inclusion criteria

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

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

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

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

Exclusion criteria

• Known history or allergy to investigational vaccine components, other preventive vaccines, or any other allergies
• Individuals with major congenital abnormalities
• Known history of immune function disorders including immunodeficiency diseases (known HIV infection in healthy participant cohorts) or other immune function disorders (all cohorts).
• 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.
• Behavioral or cognitive impairment, chronic substance abuse, or psychiatric disease or neurological disorders.
• Individuals with a known bleeding disorder.
• Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months.
• Individuals who have received other vaccines from 4 weeks prior to or within 4 weeks after any dose of the investigational product.
• Individuals with active or previous Vibrio cholerae infection.
• Individuals with receipt of a cholera vaccine in the past 5 years.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

South Africa · 5 centers

• Synergy Biomed Research Institute — Durban
• Perinatal HIV Research Unit (PHRU) — Johannesburg
• Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit — Johannesburg
• SAMRC Chatworth CRS — Durban
• SAMRC Isipingo CRS — Durban

Identifiers

NCT: NCT07304284 · IVI BIOVAC OCV-S 001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗