First in Human Phase 1 Ascending Dose Study of PanChol in Healthy Volunteers
Cholera, Cholera Vaccine Toxicity
About this trial
This is an interventional prevention trial for Cholera focused on measuring cholera, vaccine, safety, immunogenicity
Eligibility Criteria
Inclusion Criteria: Healthy adults aged from 18 to 55 years old. Considered healthy, as judged by the clinical investigator, according to medical history, physical examination, vital signs, screening laboratories, and medication history. Understanding and agreeing to comply with the study protocol including the inpatient period. Female participants must be non-pregnant and non-lactating and either 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) 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 exclusion criteria to be eligible for enrollment in the study: Confirmed or suspected immunosuppressive condition, as a result of a disease (e.g., primary immune deficiency, malignancy, HIV infection) or have taken any systemic immunosuppressive therapy within 6 months of enrollment. Pregnant or lactating women History of gastrointestinal (GI) disorder, such as previous major GI surgery, malabsorption, or any chronic GI disorders that would interfere, according to the investigator, with the IP. Acute GI or febrile illness within 7 days of enrollment. Have any acute or chronic medical condition that, in the opinion of the investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination. History of cholera vaccination History of cholera infection Abnormal stool pattern, defined as < 3 or >21 stools per week. Allergy or intolerance to PanChol or placebo component (sodium bicarbonate, lactose, ascorbic acid) Use of any systemic antibiotics within 1 month of PanChol administration Receipt of a live vaccine in the previous 4 weeks or planned in the 4 weeks following enrollment Receipt of a killed or subunit (non-live) vaccine in the previous 2 weeks or planned in the 2 weeks following enrollment. Individuals who do not speak English will not be enrolled into this trial. This study involves more than minimal risk and no prospect of direct benefit for participants. Additionally, a subject who did not speak English may not be able to easily communicate safety concerns in a timely fashion to the study investigators Childcare workers with direct contact with children ≤ 2 years of age Individuals whose occupation involves handling of food Healthcare workers who have direct contact with patients who are immunodeficient, HIV-positive, or have an unstable medical condition Use laxatives regularly Have diarrhea within 48 hours before enrollment Have a history of hypersensitivity to any of the tetracyclines Have a history of hypersensitivity to streptomycin or any aminoglycoside due to the known cross-sensitivity of patients to drugs in this class.
Sites / Locations
- Brigham and Women's Hospital Vaccine UnitRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Active Comparator
Placebo Comparator
Fixed Dose-Ranging
Adaptive Dose-finding/Optimization
Expansion module - active product
Expansion module - placebo
The first, fixed dose-ranging module utilizes a classical "3+3 design". The name is derived from the typical cohort size at a given dose [3], and the typical expansion size at that dose [3] if 1 dose-limiting side effect is observed. This module will address the uncertainty regarding the relationship between dose and adverse events (AEs). A set of pre-specified doses (log10 values 6, 7, 8, 9, and 10) will be employed, based on animal experiments and other live OCV trials. Three participants will be administered each dose (15 participants total).
A modified continual reassessment method (CRM) adaptive design will guide the dose optimization module. CRM cohorts comprise 3 participants treated concurrently at each dose. All three subjects in each cohort will receive a single dose based on the CRM model fit to all the available dose-response data.
The purpose of the expansion cohort is to gather additional clinical experience at the optimal dose of PanChol and increase the precision with which the rate of AEs is estimated. The expansion module will be randomized, double blind and placebo-controlled (20 receiving active product, 6 receiving placebo, 26 participants total).
The purpose of the expansion cohort is to gather additional clinical experience at the optimal dose of PanChol and increase the precision with which the rate of AEs is estimated. The expansion module will be randomized, double blind and placebo-controlled (20 receiving active product, 6 receiving placebo, 26 participants total).