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

Primary Purpose

Cholera, Cholera Vaccine Toxicity

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PanChol
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cholera focused on measuring cholera, vaccine, safety, immunogenicity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Arm Type

Experimental

Experimental

Active Comparator

Placebo Comparator

Arm Label

Fixed Dose-Ranging

Adaptive Dose-finding/Optimization

Expansion module - active product

Expansion module - placebo

Arm Description

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).

Outcomes

Primary Outcome Measures

The incidence of solicited and unsolicited adverse events, including serious adverse events, following PanChol vaccination.
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.

Secondary Outcome Measures

The magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae.
The stool shedding of PanChol organisms using stool cultures.

Full Information

First Posted
November 12, 2022
Last Updated
December 11, 2022
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05657782
Brief Title
First in Human Phase 1 Ascending Dose Study of PanChol in Healthy Volunteers
Official Title
PanChol-100: Safety and Immunogenicity of PanChol: First-in-Human Study of a Novel Live Attenuated Oral Cholera Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 12, 2022 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: a fixed dose-ranging module, an adaptive dose-finding/optimization module, and 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholera, Cholera Vaccine Toxicity
Keywords
cholera, vaccine, safety, immunogenicity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
53 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fixed Dose-Ranging
Arm Type
Experimental
Arm Description
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).
Arm Title
Adaptive Dose-finding/Optimization
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion module - active product
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Expansion module - placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
PanChol
Intervention Description
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 Information:
Title
The incidence of solicited and unsolicited adverse events, including serious adverse events, following PanChol vaccination.
Time Frame
180 days
Title
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
Secondary Outcome Measure Information:
Title
The magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae.
Time Frame
180 days
Title
The stool shedding of PanChol organisms using stool cultures.
Time Frame
180 days
Other Pre-specified Outcome Measures:
Title
The changes of antibodies targeting cholera specific polysaccharides.
Time Frame
180 days
Title
The changes of antibody secreting cell response.
Time Frame
180 days
Title
The stool microbiota modification according to 16S rRNA sequencing and/or metagenomics.
Time Frame
180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lindsey Baden, MD
Phone
617-525-8418
Email
lbaden@bwh.harvard.edu
Facility Information:
Facility Name
Brigham and Women's Hospital Vaccine Unit
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsey Baden, MD
Phone
617-525-7327
Email
vaccines@partners.org

12. IPD Sharing Statement

Learn more about this trial

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

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