This study is a first-in-human, Phase 1 study of the safety, tolerability, and immunogenicity of PanChol in healthy volunteers. There will be three modules in this clinical trial assessing dosing, safety, and immunogenicity: 1. a fixed dose-ranging module, 2. an adaptive dose-finding/optimization module, and 3. a placebo-controlled expansion module.
The primary objectives of this study are: * To evaluate the reactogenicity and the safety of a single-dose PanChol over a range of doses in healthy volunteers. * To evaluate the immunogenicity of a single-dose PanChol over a range of doses as measured by vibriocidal antibody titers. The secondary objectives of this study are: * To further characterize PanChol immune response, such as the magnitude of vibriocidal titers, the IgG, IgA, and IgM antibodies targeting Inaba- and Ogawa-specific polysaccharides, cholera toxin B subunit, and TCP, IgA- and IgG-antibody secreting cell responses (ALS/plasmablast responses) and/or the memory B cell (MBC) response. * To characterize the stool shedding of the PanChol organisms after vaccination. * To evaluate the changes of the gut microbiota after PanChol vaccination and to compare these changes with cholera-induced changes on microbiota Participants will be enrolled at the Brigham and Women's Hospital (BWH). For the first days of the trial, participants will be inpatients in BWH, for optimal safety monitoring and for fecal and blood samples collection. PanChol or placebo will be administered on Day 1. On Day 6, participants will be starting doxycycline to eradicate the shedding of the vaccine organisms. On Day 7, those who are no longer excreting PanChol in their stool will be discharged. After discharge, volunteers will return on days 15, 29, 57, and 180 for monitoring of general health, AE assessment, immune responses, and fecal microbiota composition. Approximately 53 adult healthy volunteers are planned to be enrolled in this study if all planned treatment groups are conducted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
53
PanChol is a new second generation live-attenuated oral cholera vaccine (OCV) that circumvents limitations of previous live-attenuated OCVs. In contrast to other live OCVs, PanChol is derived from a current circulating pandemic V. cholerae strain, thus eliminating the risk of vaccine-derived genes from extinct V. cholerae strains (such as CVD 103-HgR) recombining with circulating V. cholerae strains.
Brigham and Women's Hospital Vaccine Unit
Boston, Massachusetts, United States
RECRUITINGThe incidence of solicited and unsolicited adverse events, including serious adverse events, following PanChol vaccination.
Time frame: 180 days
The seroconversion (4-fold rise titer over baseline) of the vibriocidal titers to both Inaba and Ogawa V. cholerae between pre- and post-vaccination with PanChol.
Time frame: 180 days
The magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae.
Time frame: 180 days
The stool shedding of PanChol organisms using stool cultures.
Time frame: 180 days
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