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.

Study Overview

• Status: Recruiting
• Conditions: Cholera Vaccination
• Intervention / Treatment: Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Biological: Active Comparator, Euvichol®-Plus

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.

• Study Type: Interventional
• Enrollment (Estimated): 2824
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dr. Naveena D'Cor Project Technical Lead / Study Medical Monitor, MD; Phone Number: +82 2 8811 000; Email: naveena.dcor@ivi.int
• Study Contact Backup: Name: Beverley Cowper Medical Consultant, MD; Email: BeverleyC@biovac.co.za

Study Locations

• South Africa
  • Eastern Cape
    • Durban, Eastern Cape, South Africa, 5201
      • Not yet recruiting
      • Synergy Biomed Research Institute
      • Contact: Mookho Malahleha Principal Investigator; Phone Number: 0437222306; Email: drmookho@sbri.org.za
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Recruiting
      • Perinatal HIV Research Unit (PHRU)
      • Contact: Ravindre Panchia Principal Investigator; Phone Number: 011-989-9711; Email: panchiar@phru.co.za
    • Johannesburg, Gauteng, South Africa, 1862
      • Not yet recruiting
      • Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit
      • Contact: Christopher Stavrou Principal Investigator; Phone Number: +27 11 983 4283; Email: christopher.stavrou@wits-vida.org
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4092
      • Recruiting
      • SAMRC Chatworth CRS
      • Contact: Logashvari Naidoo Principal Investigator; Phone Number: 0314014150; Email: logashvari.naidoo@mrc.ac.za
    • Durban, KwaZulu-Natal, South Africa, 4110
      • Not yet recruiting
      • SAMRC Isipingo CRS
      • Contact: Vimla Naicker Principal Investigator; Phone Number: 0319027494; Email: vimla.naicker@mrc.ac.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A1: Biovac OCV-S; Biovac OCV-S (Lot 1), HIV Negative Group, 18-45 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Experimental: Arm A2: Biovac OCV-S; Biovac OCV-S (Lot 2), HIV Negative Group, 18-45 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Experimental: Arm A3: Biovac OCV-S; Biovac OCV-S (Lot 3), HIV Negative Group, 18-45 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Active Comparator: Arm A4: Euvichol®-Plus; Euvichol®-Plus, HIV Negative Group, 18-45 years	Biological: Active Comparator, Euvichol®-Plus; Two doses (1.5mL) at two weeks interval given orally.
Experimental: Arm B1: Biovac OCV-S; Biovac OCV-S, HIV Negative Group, 6-17 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Active Comparator: Arm B2: Euvichol®-Plus; Euvichol®-Plus, HIV Negative Group, 6-17 years	Biological: Active Comparator, Euvichol®-Plus; Two doses (1.5mL) at two weeks interval given orally.
Experimental: Arm C1: Biovac OCV-S; Biovac OCV-S, HIV Negative Group, 1-5 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Active Comparator: Arm C2: Euvichol®-Plus; Euvichol®-Plus, HIV Negative Group, 1-5 years	Biological: Active Comparator, Euvichol®-Plus; Two doses (1.5mL) at two weeks interval given orally.
Experimental: Arm AA1: Biovac OCV-S; Biovac OCV-S, People living with HIV, 18-45 years	Biological: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine); Two doses (1.5mL) at two weeks interval given orally.
Active Comparator: Arm AA2: Euvichol®-Plus; Euvichol®-Plus, People living with HIV, 18-45 years	Biological: Active Comparator, Euvichol®-Plus; Two doses (1.5mL) at two weeks interval given orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa	Proportion of participants showing seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa (seroconversion is defined as at least 4-fold increase of vibriocidal titers compared to baseline) at 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus for all ages, in the HIV negative group.	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	Safety of each investigational product dose at a specified duration in the HIV negative group: Occurrence of any Serious Adverse Event (SAE)/ Adverse Event of Special Interest (AESI)/ Medically Attended Adverse Event (MAAE) from the first dose vaccination throughout the final study visit; Occurrence of immediate adverse events within 30 minutes after each dose vaccination; Occurrence of solicited adverse events within 7 days after each dose vaccination; Occurrence of unsolicited adverse events within 14 days after each dose vaccination	Within 14 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants showing seroconversion against Vibrio cholerae O1 Inaba and Ogawa	The proportion of participants showing seroconversion against Vibrio cholerae O1 Inaba and Ogawa 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus in each age stratum, in the HIV negative group.	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	GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus in each age stratum, in the HIV negative group.	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	GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa 2 weeks after second dose of 3 lots of Biovac OCV-S in adults in the HIV negative group.	2 weeks after second dose of 3 lots of Biovac OCV-S
Geometric Mean Titer (GMT) of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa for all ages	GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus for all ages, in the HIV negative group.	2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants showing seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and Ogawa	The proportion of participants showing seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and Ogawa 2 weeks after second dose of 3 lots of Biovac OCV-S in adults in the HIV negative group.	2 weeks after second dose of 3 lots of Biovac OCV-S
Seroconversion rate and GMT of vibriocidal antibodies	Seroconversion rate and GMT of vibriocidal antibodies 2 weeks after first dose of either Biovac OCV-S or Euvichol®-Plus for all ages and for each age stratum, in the HIV negative group.	2 weeks after first dose of either Biovac OCV-S or Euvichol®-Plus
Seroconversion rate and GMT of vibriocidal antibodies	Seroconversion rate and GMT of vibriocidal antibodies 2 weeks after one and two doses of Biovac OCV-S and Euvichol®-Plus for adults, in the PLWH group.	2 weeks after one and two doses of Biovac OCV-S and Euvichol®-Plus
Incidence of Treatment-Emergent Adverse Events in the PLWH group	Safety of each investigational product dose at a specified duration in the PLWH group: Occurrence of any SAE/AESI/MAAE from the first dose vaccination throughout the final study visit; Occurrence of immediate adverse events within 30 minutes after each dose vaccination; Occurrence of solicited adverse events within 7 days after each dose vaccination; Occurrence of unsolicited adverse events within 14 days after each dose vaccination	Within 14 days after each dose vaccination

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: Medical Research Council, South Africa; BioVac
• Investigators: Principal Investigator: Tarun Saluja, MD, International Vaccine Institute; Principal Investigator: Glenda Gray, MD, Medical Research Council, South Africa; Study Director: Julia Lynch, MD, International Vaccine Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Estimated): December 26, 2025

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Biovac OCV-S; Euvichol®-Plus; IVI BIOVAC OCV-S 001; International Vaccine Institute (IVI); Biovac Institute; South African Medical Research Council (SAMRC)
• Additional Relevant MeSH Terms: Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Cholera Vaccines
• Other Study ID Numbers: IVI BIOVAC OCV-S 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No