Recruiting
Phase 1

PanChol

Sponsor:

Brigham and Women's Hospital

Code:

NCT05657782

Conditions

Cholera

Cholera Vaccine Toxicity

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Accepted

Interventions

PanChol

Study Details

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.

Conditions

Cholera

Cholera Vaccine Toxicity

Study ID

NCT05657782

Start date

Dec 12, 2022

Status verified date

Dec, 2022

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Dec 1, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Accepted

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 exclusion criteria to be eligible for enrollment in the study:

1. 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.
2. Pregnant or lactating women
3. 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.
4. Acute GI or febrile illness within 7 days of enrollment.
5. 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.
6. History of cholera vaccination
7. History of cholera infection
8. Abnormal stool pattern, defined as < 3 or >21 stools per week.
9. Allergy or intolerance to PanChol or placebo component (sodium bicarbonate, lactose, ascorbic acid)
10. Use of any systemic antibiotics within 1 month of PanChol administration
11. Receipt of a live vaccine in the previous 4 weeks or planned in the 4 weeks following enrollment
12. Receipt of a killed or subunit (non-live) vaccine in the previous 2 weeks or planned in the 2 weeks following enrollment.
13. 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
14. Childcare workers with direct contact with children ≤ 2 years of age
15. Individuals whose occupation involves handling of food
16. Healthcare workers who have direct contact with patients who are immunodeficient, HIV-positive, or have an unstable medical condition
17. Use laxatives regularly
18. Have diarrhea within 48 hours before enrollment
19. Have a history of hypersensitivity to any of the tetracyclines
20. Have a history of hypersensitivity to streptomycin or any aminoglycoside due to the known cross-sensitivity of patients to drugs in this class.

Study Design

Enrollment

53 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Fixed Dose-Ranging

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).

experimental: Adaptive Dose-finding/Optimization

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.

active comparator: Expansion module - active product

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).

placebo comparator: Expansion module - placebo

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).

Interventions

PanChol

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.

Primary outcome measure

  • The 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 ]

Central Contacts and Locations

Central contacts

Locations

Brigham and Women's Hospital Vaccine Unit

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Dec 20, 2022

Last verified

Dec, 2022

Keywords

  • cholera
  • vaccine
  • safety
  • immunogenicity

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2022-12-20.