Extended Dosing Intervals Trial for Oral Cholera Vaccine, Kenya

NCT07487077 | Recruiting Phase 4 DMC

• 2 other identifiers: Sabin-OCV-24Wellcome Grant Number: 228242/
• Study Type: interventional
• Target: 1,071
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cholera Vaccination

Keywords

Cholera; extended dosing; Euvichol-S; OCV; vaccination; immunization

Outcome Measures

Primary Outcomes (1)

• To assess and compare the immune response to Euvichol-S, measured by plasma vibriocidal geometric mean titer (GMT) two weeks after the second vaccine dose, across different dosing intervals in participants aged 1 year and older.

  Plasma Vibriocidal GMT Measurement: Measurement of the concentration of plasma vibriocidal GMT two weeks after administering the second dose of Euvichol-S. Vibriocidal antibodies are the best-established immune correlate of protection against cholera. The GMT, a statistical representation of the antibody levels in the study population, is an objective and quantifiable measure of the vaccine's immunogenicity. By comparing GMT values across different dosing intervals, we aim to validate the immunogenicity of extended dosing schedules, assessing if they are as effective at eliciting a protective immune response as the standard two-week interval. This assessment will be crucial in guiding future vaccination strategies, particularly in resource-limited settings where scheduling flexibility can significantly impact public health outcomes.

  Plasma vibriocidal GMT measurement 2-weeks after the 2nd vaccine dose of Euvichol-S in participants 1+ years for the Comparator Arm (2nd dose at 2 weeks), Intervention Arm 1 (2nd dose at 3-months), and Intervention Arm 2 (2nd dose at 1-year)

Secondary Outcomes (1)

• Plasma Vibriocidal GMT

  Plasma vibriocidal GMT over an 18-month period: two weeks post-vaccination and also at 6, 12, and 18 months post-enrollment.

Other Outcomes (4)

• Exploratory Objective 1 - Anti-O-specific polysaccharide (OSP) IgA responses in plasma

  Anti-OSP IgA over an 18-month period: two weeks post-vaccination and also at 6, 12, and 18 months post-enrollment.

• Exploratory Objective 2 - Anti-O-specific polysaccharide (OSP) IgG responses in plasma

  Anti-OSP IgG over an 18-month period: two weeks post-vaccination and also at 6, 12, and 18 months post-enrollment.

• Exploratory Objective 3 - PBMC Sub-cohort: Circulating gut-homing anti-OSP memory B cells (MBCs)

  MBC at baseline, 14 days after 2nd dose, and 12 months after 1st dose (1-year interval group) in sub-cohort of children 1-14 years.

Study Arms (3)

Standard Dosing Arm (Two Weeks Interval)

ACTIVE COMPARATOR

Participants received the second OCV dose per the recommended dosing schedule 2 weeks after the initial dose.

Drug: Euvichol-S Oral Cholera Vaccine

Extended Interval Dosing Arm (Three Months Interval)

EXPERIMENTAL

Participants received the second OCV dose 3 months after the initial dose.

Drug: Euvichol-S Oral Cholera Vaccine

Annual Booster Dosing Arm (Twelve Months Interval)

EXPERIMENTAL

Participants received the second OCV dose 12 months after the initial dose.

Drug: Euvichol-S Oral Cholera Vaccine

Interventions

Euvichol-S Oral Cholera Vaccine DRUG

Parallel-group, phase IV, open-label, randomized, non-inferiority trial Arms: Three distinct arms, each balanced in a 1:1:1 ratio: Standard Dosing Arm (Two Weeks Interval) Extended Interval Dosing Arm (Three Months Interval) Annual Booster Dosing Arm (Twelve Months Interval) Each dosing arm will have the following three age strata: Children aged 1-4 years Children aged 5-14 years Adults aged 15 years and older

Also known as: cholera: inactivated oral, Euvichol

Annual Booster Dosing Arm (Twelve Months Interval); Extended Interval Dosing Arm (Three Months Interval); Standard Dosing Arm (Two Weeks Interval)

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Residents of Mukuru, Nairobi, Kenya
• Individuals aged 1 year and above
• Voluntary written informed consent for study participation provided by an individual or his/her legally acceptable representative. Children aged 13 years and above will also provide assent, with parental permission required for all children.
• Ability to comply with study requirements and attend follow-up visits during the study period.
• Participants must be in good health, as determined by medical history, physical examination, and the clinical judgment of the investigators. Clinical judgment will consider factors such as the absence of acute illness or, uncontrolled or severe chronic conditions that may affect participation in the study.
• Lactating women may be enrolled following clinical assessment and informed consent. The vaccine contains killed, formalin-inactivated bacteria that are not systemically absorbed and act locally in the gastrointestinal tract.

You may not qualify if:

• Known history of hypersensitivity reactions to other vaccines.
• Pregnant women, due to differences in immune response. A pregnancy test will be administered to all female participants who have reached menarche and are under 50 years.
• Reported diarrhea or abdominal pain lasting 2 weeks or longer within 6 months prior to study initiation; to avoid confounding the vaccine's effects with pre-existing conditions.
• Received a cholera vaccine in the last 24 months: Ensures that the study assesses the vaccine in question without interference from prior vaccinations.
• History of cholera disease in the last 24 months: Recent history of cholera infection can interfere with the measurement of vaccine response.
• Severely malnourished individuals as determined by mid-upper arm circumference (MUAC) and age-specific body mass index (BMI) measurements: malnutrition can affect immune response and vaccine efficacy. In children below 510 years, severe malnutrition will be defined as MUAC \< 11.5 cm, for older children (age 5 - 17y) severe malnutrition will be defined as BMI-for-age z score \< -3 (WHO Child Growth Standards), for children \<10y, presence of bilateral pitting oedema will be considered indicative of severe malnutrition. For adults (18y and above), severe malnutrition will be while in older children and adults it will be defined as BMI \< 16.
• Non-HIV/AIDS immunosuppressive condition or on immunosuppressive therapy: Such conditions can significantly alter vaccine response.
• Presence of bleeding disorders or medical contraindication for blood draws: To ensure participant safety during blood collection.
• Participation in another clinical trial with investigational product dosing within 6 months prior to study initiation.
• An individual thought to have difficulty in participating in the study due to severe chronic diseases, based on the judgment of the investigator.
• An individual thought to have difficulty participating in the study due to reasons, such as significant logistical constraints, or communication barriers, or likely to be away for a period of at least 3 consecutive months in the first 6 months of enrollment based on the judgment of the investigator.

Sponsors & Collaborators

• Albert B. Sabin Vaccine Institute: lead
• Kenya Medical Research Institute: collaborator
• Washington State University: collaborator
• Massachusetts General Hospital: collaborator
• Kenya Ministry of Health: collaborator
• Nairobi City County: collaborator

Study Sites (1)

KEMRI

Nairobi, Kenya

RECRUITING

MeSH Terms

Conditions

Cholera

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Central Study Contacts

Samuel Kariuki, BVM, PhD

CONTACT

+254 722232467; samkariuki2@gmail.com

Cecilia Mbae, PhD

CONTACT

+254 722485819; cmkathure@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel-group, phase IV, open-label, randomized, non-inferiority trial Arms: Three distinct arms, each balanced in a 1:1:1 ratio: Standard Dosing Arm (Two Weeks Interval) Extended Interval Dosing Arm (Three Months Interval) Annual Booster Dosing Arm (Twelve Months Interval) Each dosing arm will have the following three age strata: Children aged 1-4 years Children aged 5-14 years Adults aged 15 years and older

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 23, 2026
• Study Start: October 31, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

KE (1)