DOI: 10.12688/wellcomeopenres.27519.1 ISSN: 2398-502X

A phase IV parallel-group, open-label, randomized non-inferiority trial evaluating immunogenicity of extended dosing intervals for Euvichol-S oral cholera vaccine in Nairobi, Kenya: study protocol for a randomized non-inferiority trial

Eric Osoro, Cecilia Mbae, Kate Doyle, Kering Kimutai, Catherine Kiama, Isaac Ngere, Bryan O. Nyawanda, Luci Keter Kipkoech, Cynthia Ombok, Diana Imoli, Mercy Ngetich, Shamsa Mohammed Haji, Mary Kariuki, Peter Muturi, Shingo Inoue, Alice S. Carter, Jessica C. Seidman, Richelle Charles, Samuel Kadivane, Emmanuel Okunga, Caroline Ngunu, Denise Garrett, Samuel Kariuki
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Background Global shortages of oral cholera vaccine have led to widespread use of single-dose vaccination. Although this approach increases immediate population coverage, protection may be less durable and effectiveness is lower in young children. Evidence remains limited on whether extending the interval before the second dose of Euvichol-S preserves the immune response achieved with the recommended two-week schedule. Protocol This phase IV, parallel-group, open-label, randomized non-inferiority trial is being conducted in Mukuru, Nairobi, Kenya. A total of 1,071 participants aged ≥1 year are being randomized 1:1:1 to receive a second Euvichol-S dose after two weeks, three months, or twelve months. Randomization is stratified by age group: 1–4 years, 5–14 years, and ≥ 15 years. The respective permitted dose-2 windows are Days 11–17, Days 83–97, and Days 351–379. The primary outcome is the plasma vibriocidal antibody response against Vibrio cholerae O1 Inaba and Ogawa, measured 14 days after the second dose. Each extended schedule will be compared with the two-week schedule within each age group using a geometric mean titre ratio and a non-inferiority margin of 0.90. The primary analysis will use the per-protocol population, with intention-to-treat analyses conducted as sensitivity analyses. Secondary outcomes include seroconversion, persistence of vibriocidal responses, laboratory-confirmed cholera, and safety. A paediatric peripheral blood mononuclear cell sub-cohort is evaluating plasmablast and memory B-cell responses. Discussion The trial will provide evidence on whether longer intervals before the second Euvichol-S dose preserve vaccine-induced immune responses across age groups. Because the primary outcome is immunological, implications for clinical protection and vaccination policy will require cautious interpretation. Trial registration: Pan African Clinical Trials Registry, PACTR202501835187008. Registered 28 January 2025.

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