PanChol Vaccine for Cholera

Overseen By Lindsey Baden, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Immunosuppressants, Antibiotics, Tetracyclines, Aminoglycosides

Disqualifiers: Immunosuppressive condition, GI disorder, Cholera history, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 7 days

53 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you've used systemic antibiotics within a month before the trial or received certain vaccines recently.

What data supports the effectiveness of the PanChol Vaccine for cholera?

Research on similar oral cholera vaccines, like Shanchol, shows they can provide significant protection against cholera, with one study indicating 65% protection over five years. This suggests that vaccines like PanChol could also be effective in preventing cholera. ^{1 2 3 4 5}

How is the PanChol Vaccine for cholera different from other treatments?

The PanChol Vaccine for cholera is unique because it is a new treatment option, whereas existing vaccines like Shanchol and Dukoral are already used to prevent cholera. Unlike these existing vaccines, PanChol may offer a different mechanism of action, administration route, or formulation, but specific details are not provided in the available research. ^{1 2 6 7 8}

Eligibility Criteria

Healthy adults aged 18-55 can join this trial. They must be in good health based on medical checks, agree to stay in the hospital when needed, and use reliable contraception or abstain from sex if they can have children. People with immune issues, recent GI illness, previous cholera vaccine or infection, abnormal stool patterns, allergies to PanChol/placebo ingredients, recent antibiotic use or vaccines cannot join.

Inclusion Criteria

Understanding and agreeing to comply with the study protocol including the inpatient period

I am considered healthy based on my recent medical exams and history.

I am not pregnant or breastfeeding, and if of childbearing age, I am using effective birth control.

Exclusion Criteria

I have not had a fever or stomach illness in the last week.

I haven't taken any antibiotics in the last month.

I regularly use laxatives.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of PanChol or placebo and are monitored as inpatients for safety and sample collection

7 days

Inpatient stay at BWH

Follow-up

Participants are monitored for general health, adverse events, immune responses, and fecal microbiota composition

180 days

Visits on days 15, 29, 57, and 180

Extension

Optional continuation for further monitoring and data collection

Treatment Details

Interventions

• PanChol

Trial Overview The study is testing a new cholera vaccine called PanChol. It's done in three parts: figuring out the right dose range; finding the best dose; and comparing it with a placebo (a treatment with no active drug). Volunteers will get either PanChol or placebo to check for safety and how well their bodies respond.

Participant Groups

Group I: Fixed Dose-Ranging Experimental Treatment 1 Intervention

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).

Group II: Adaptive Dose-finding/Optimization Experimental Treatment 1 Intervention

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.

Group III: Expansion module - active product Active Control 1 Intervention

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).

Group IV: Expansion module - placebo Placebo Group 1 Intervention

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).

PanChol is already approved in European Union, United States for the following indications:

Approved in European Union as PanChol for:

• Prevention of cholera

Approved in United States as PanChol for:

• Prevention of cholera

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

In a matched case-control study in Guinea involving 40 cholera cases and 160 controls, the two-dose Shanchol vaccine demonstrated significant short-term effectiveness, providing 86.6% protection against cholera after adjustment for confounding factors.

The results support the use of Shanchol as part of integrated responses to cholera outbreaks and highlight the importance of establishing a cholera vaccine stockpile for emergency situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Vibrio cholerae vaccine in an outbreak in Guinea. Luquero, FJ., Grout, L., Ciglenecki, I., et al.[2022]

The oral cholera vaccine Shanchol demonstrated a protective effectiveness of 69% against cholera for individuals receiving two doses, which aligns with previous clinical trial results, indicating its efficacy in real-world settings.

The study, conducted in a cholera-endemic area of India, involved over 31,000 residents and showed that even a single dose of the vaccine provided some protection (33%), supporting its use in public health campaigns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India. Wierzba, TF., Kar, SK., Mogasale, VV., et al.[2022]

The bivalent whole-cell oral cholera vaccine (Shanchol) effectively induced significant mucosal immune responses, as evidenced by increased antibody secreting cells (ASCs) specific to V. cholerae O1 antigens in 24 Haitian adults after the first dose.

The second dose of the vaccine did not significantly boost ASC responses, indicating that the current two-dose schedule may not be optimal for enhancing mucosal immunity in adults living in cholera-endemic regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults. Matias, WR., Falkard, B., Charles, RC., et al.[2021]

The oral cholera vaccine, which includes a nontoxic B subunit of cholera toxin and killed cholera vibrios, has been shown to provide effective protection against cholera for at least 3 years without any side effects, based on extensive clinical trials.

This vaccine also offers some protection against diarrhea caused by enterotoxinogenic E. coli (ETEC), and advancements in recombinant DNA techniques suggest that a new effective oral ETEC vaccine may soon be developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of oral vaccines against cholera and enterotoxinogenic Escherichia coli diarrhea. Holmgren, J., Svennerholm, AM.[2006]

Euvichol-Plus demonstrated non-inferior immunogenicity compared to Shanchol, with 68.93% of participants showing a significant increase in antibodies against cholera after vaccination, indicating it is an effective alternative vaccine.

The safety profile of Euvichol-Plus was comparable to Shanchol, with headache being the most common side effect, suggesting it is a safe option for both adults and children in India.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children: an open-label, randomised, multicentre, non-inferiority, parallel-group, phase 3 trial. Shah, S., Nandy, RK., Sethi, SS., et al.[2023]

The oral cholera vaccine Shanchol was found to be safe, with no major adverse events reported across all age groups (adults, toddlers, and younger children) in a double-blind, randomized placebo-controlled study.

Immunogenicity results showed strong vibriocidal antibody responses, particularly in toddlers (84% against Vibrio cholerae O1 Inaba), indicating that Shanchol effectively stimulates the immune system and supports its potential for use in cholera-endemic regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age. Saha, A., Chowdhury, MI., Khanam, F., et al.[2022]

The oral cholera vaccine Shanchol™ remains safe and effective even when stored at elevated temperatures (up to 42°C) for 14 days, as shown in a study with 580 adult participants across four groups.

All groups demonstrated significant immune responses to the vaccine, with no major differences in safety or immunogenicity, suggesting that Shanchol™ can be distributed more easily in resource-poor settings without the need for strict cold chain storage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The oral cholera vaccine Shanchol™ when stored at elevated temperatures maintains the safety and immunogenicity profile in Bangladeshi participants. Saha, A., Khan, A., Salma, U., et al.[2022]

Cholera remains a significant health issue in Africa and Asia, with two effective oral vaccines available: Dukoral, which offers additional short-term protection against E. coli, and Shanchol, both recommended for use in endemic areas and for travelers.

The systematic review of vaccine efficacy and acceptance supports the use of these vaccines in cholera-affected populations, highlighting their importance in preventing outbreaks and protecting at-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination strategies to combat an infectious globe: oral cholera vaccines. López-Gigosos, RM., Plaza, E., Díez-Díaz, RM., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of Vibrio cholerae vaccine in an outbreak in Guinea. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Development of oral vaccines against cholera and enterotoxinogenic Escherichia coli diarrhea. [2006]

5. England pubmed.ncbi.nlm.nih.gov

Comparison of the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children: an open-label, randomised, multicentre, non-inferiority, parallel-group, phase 3 trial. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The oral cholera vaccine Shanchol™ when stored at elevated temperatures maintains the safety and immunogenicity profile in Bangladeshi participants. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Vaccination strategies to combat an infectious globe: oral cholera vaccines. [2021]