First in Human Phase 1 Ascending Dose Study of PanChol in Healthy Volunteers

NCT05657782 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: PanChol-100
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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. 1.a fixed dose-ranging module,
2. 2.an adaptive dose-finding/optimization module, and
3. 3.a placebo-controlled expansion module.

Conditions

Cholera; Cholera Vaccine Toxicity

Keywords

cholera; vaccine; safety; immunogenicity

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• The magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae.

  180 days

• The stool shedding of PanChol organisms using stool cultures.

  180 days

Other Outcomes (3)

• The changes of antibodies targeting cholera specific polysaccharides.

  180 days

• The changes of antibody secreting cell response.

  180 days

• The stool microbiota modification according to 16S rRNA sequencing and/or metagenomics.

  180 days

Study Arms (4)

Fixed Dose-Ranging

EXPERIMENTAL

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).

Biological: PanChol

Adaptive Dose-finding/Optimization

EXPERIMENTAL

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.

Biological: PanChol

Expansion module - active product

ACTIVE COMPARATOR

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).

Biological: PanChol

Expansion module - placebo

PLACEBO COMPARATOR

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).

Biological: PanChol

Interventions

PanChol BIOLOGICAL

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.

Adaptive Dose-finding/Optimization; Expansion module - active product; Expansion module - placebo; Fixed Dose-Ranging

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital Vaccine Unit

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (1)

• Leitner DR, Walsh SR, Suzuki M, Desjardins M, Hannaford A, Sherman AC, Levine H, Carr L, Hammerness E, Osaki A, Sullivan E, Wang B, Balazs GI, Park Chang JB, Slater DM, Puri N, Kuehl CJ, Chen WH, Harris JB, Piantadosi S, Baden LR, Waldor MK; PanChol study group. Safety and immunogenicity of PanChol, a single-dose live-attenuated oral cholera vaccine: results from a phase 1a, double-blind, randomised, placebo-controlled trial. Lancet Infect Dis. 2026 Jan 7:S1473-3099(25)00682-6. doi: 10.1016/S1473-3099(25)00682-6. Online ahead of print.

  PMID: 41519137 DERIVED

MeSH Terms

Conditions

Cholera

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Central Study Contacts

Lindsey Baden, MD

CONTACT

617-525-8418; lbaden@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Infectious Diseases

Study Record Dates

• First Submitted: November 12, 2022
• First Posted: December 20, 2022
• Study Start: December 12, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

US (1)