Cholera, Cholera Vaccine Toxicity
Conditions
Keywords
cholera, vaccine, safety, immunogenicity
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALPanChol
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.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adults aged from 18 to 55 years old. 2. Considered healthy, as judged by the clinical investigator, according to medical history, physical examination, vital signs, screening laboratories, and medication history. 3. Understanding and agreeing to comply with the study protocol including the inpatient period. 4. Female participants must be non-pregnant and non-lactating and either 1. surgically sterile (history of bilateral ligation, bilateral salpingectomy, bilateral oophorectomy, total hysterectomy) or postmenopausal (defined as as amenorrhea for at least 12 consecutive months before screening without an alternative medical cause) 2. be of child-bearing potential and practicing an acceptable method of contraception or abstaining from all activities that could result in pregnancy for at least 28 days before vaccination until 3 months after receiving the IP. Acceptable methods of contraception include barrier methods (such as condom, diaphragm, or cervical cap used in conjunction with spermicide), intrauterine device, hormonal contraception (that may be taken or administered by oral, intravaginal, transdermal, subdermal or IM route), vasectomized partner (the vasectomized partner should be the sole partner for that participant).
Exclusion criteria
Each participant must not meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of solicited and unsolicited adverse events, including serious adverse events, following PanChol vaccination. | 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. | 180 days |
Secondary
| Measure | Time frame |
|---|---|
| The stool shedding of PanChol organisms using stool cultures. | 180 days |
| The magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae. | 180 days |
Other
| Measure | Time frame |
|---|---|
| The stool microbiota modification according to 16S rRNA sequencing and/or metagenomics. | 180 days |
| The changes of antibodies targeting cholera specific polysaccharides. | 180 days |
| The changes of antibody secreting cell response. | 180 days |
Countries
United States
Contacts
Primary ContactLindsey Baden, MD
Outcome results
None listed