What this Trial Is About

Background: Despite efforts to control cholera, outbreaks continue to occur in Kenya. Oral cholera vaccines (OCVs) are a critical tool in cholera prevention strategies. This study evaluates the immunogenicity of extended dosing intervals for Euvichol-S, a WHO-prequalified OCV, in a Phase IV non-inferiority trial. Overview Design: This trial is a parallel-group, open-label, randomized, non-inferiority study. It aims to compare the immune response of three dosing schedules of the Euvichol-S OCV: a standard 2-week interval, a 2-month interval, and a 12-month interval. The study will enroll 1071 participants, stratified by age into three groups (1-4 years, 5-14 years, 15+ years. The primary endpoint is the plasma vibriocidal geometric mean titer (GMT) measured two weeks after the second dose. Primary Objective: To assess and compare the immune response to Euvichol-S measured by vibriocidal GMT two weeks after the second vaccine dose across different dosing intervals. Study Sites: The study will be conducted in the Mukuru informal settlement in Nairobi, Kenya, a high-priority cholera hotspot area. The Kenya Medical Research Institute (KEMRI) will manage the study, leveraging its established relationship with the community. Study Population: Inclusion criteria include residents of Mukuru ≥1 year, who are healthy as determined by medical history and physical examination. Exclusion criteria include pregnant women, severe malnutrition, and non-HIV immunosuppressive conditions or severe chronic diseases. Study Interventions: Participants will be randomized to one of three dosing arms stratified by age: a standard 2-week interval, a 3-month interval, or an annual booster interval. Participants will receive the Euvichol-S OCV according to the assigned schedule. The follow-up period for participants will be 18 months, during which they will undergo regular scheduled visits and additional unscheduled visits as needed (i.e., standard dosing arm: six scheduled visits; 3-month interval arm: 7 visits; annual booster arm: 6 visits). Blood samples will be collected at each vaccination visit and 14 days later and at 6 months, 1 year and 18 months after enrollment to measure plasma vibriocidal GMT and other immunological markers. Older children in the PBMC cohort will have two additional samples collected five days after each vaccine dose and a larger blood volume (10mls) collected at 14 days after the second dose. Outcome Measures: Primary outcome measures include the plasma vibriocidal GMT two weeks post-second dose. Secondary outcomes include antibody seroconversion rates, longitudinal GMT changes, incidence of cholera disease, and the safety profile of the vaccine. The PBMC sub-cohort will provide detailed insights into memory B cell and plasmablast responses. Sample Size: The study will enroll 1071 participants with equal distribution across the three dosing arms and age strata. The PBMC sub-cohort will include 240 participants (40 per arm among 5-14 years, 40 per arm 1-4 years), with detailed immunological assessments. Data Analysis: The immunogenicity of the vaccine across different dosing schedules will be compared to determine non-inferiority. Data will be analyzed descriptively to summarize the by-grade incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and other safety indicators. Impact: This trial aims to generate evidence on the optimal dosing schedule for Euvichol-S OCV, potentially informing future vaccination strategies in cholera-endemic regions and improving cholera prevention in resource-limited settings.

Extended Dosing Intervals Trial for Oral Cholera Vaccine, Kenya