Cholera Vaccination
Conditions
Keywords
Biovac OCV-S, Euvichol®-Plus, IVI BIOVAC OCV-S 001, International Vaccine Institute (IVI), Biovac Institute, South African Medical Research Council (SAMRC)
Brief summary
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
BIOLOGICALExperimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine)
Two doses (1.5mL) at two weeks interval given orally.
BIOLOGICALActive Comparator, Euvichol®-Plus
Two doses (1.5mL) at two weeks interval given orally.
Sponsors
BioVac
Medical Research Council, South Africa
International Vaccine Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa | 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 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. |
| Incidence of Treatment-Emergent Adverse Events in the HIV negative group | Within 14 days after each vaccination | Safety of each investigational product dose at a specified duration in the HIV negative group: 1. 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 2. Occurrence of immediate adverse events within 30 minutes after each dose vaccination 3. Occurrence of solicited adverse events within 7 days after each dose vaccination 4. Occurrence of unsolicited adverse events within 14 days after each dose vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Geometric Mean Titer (GMT) of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa for all ages | 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 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. |
| GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in each age stratum | 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 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. |
| GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in adults | 2 weeks after second dose of 3 lots of Biovac OCV-S | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion rate and GMT of vibriocidal antibodies | 2 weeks after first dose of either Biovac OCV-S or Euvichol®-Plus | 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. |
| 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 | 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. |
| Incidence of Treatment-Emergent Adverse Events in the PLWH group | Within 14 days after each dose vaccination | Safety of each investigational product dose at a specified duration in the PLWH group: 1. Occurrence of any SAE/AESI/MAAE from the first dose vaccination throughout the final study visit 2. Occurrence of immediate adverse events within 30 minutes after each dose vaccination 3. Occurrence of solicited adverse events within 7 days after each dose vaccination 4. Occurrence of unsolicited adverse events within 14 days after each dose vaccination |
Countries
South Africa
Contacts
Primary ContactDr. Naveena D'Cor Project Technical Lead / Study Medical Monitor, MD
Backup ContactBeverley Cowper Medical Consultant, MD
Outcome results
None listed