VENBETA6890 for Diarrhea

(MBL-ETEC-21-01 Trial)

Overseen By Sponsor Investigator, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Mark Klempner

Must not be taking: Laxatives, Antibiotics, Steroids, others

Disqualifiers: Pregnancy, IgA deficiency, Immunosuppression, others

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking any prescription and over-the-counter medications, traditional Chinese medicine, herbal medicine, vitamins, minerals, and other dietary supplements at least 14 days before the study and throughout its duration. If you are on any medications that might affect immune function, you must stop them 30 days before the study.

How is the drug VENBETA6890 different from other treatments for diarrhea?

The drug VENBETA6890 may be unique due to its potential mechanism of action as a 5-HT3 receptor antagonist, similar to ramosetron and KB-R6933, which are known to inhibit diarrhea induced by certain triggers. This class of drugs is not widely used yet, making VENBETA6890 potentially novel in its approach to treating diarrhea. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a phase 1, randomized, placebo-controlled, blinded study in up to 36 healthy adults, aged 18-45 years, challenged with Enterotoxigenic Escherichia coli, evaluating the safety, tolerability and anti-diarrheal activity of VENBETA6890, an orally administered, human monoclonal IgA.

Research Team

Sponsor Investigator, MD

Principal Investigator

University of Massachusetts, Worcester

Eligibility Criteria

This trial is for healthy adults aged 18-45 who can participate in a study where they will be exposed to E. coli bacteria to test a new treatment. People with certain health conditions or on conflicting medications are likely excluded, but specific criteria aren't provided.

Inclusion Criteria

Provide written informed consent before initiation of any study procedures

Willing and able to complete all study requirements, restrictions, confinement to the Research Isolation ward, visits and procedures

I am either not able to have children, practice abstinence, or use effective birth control.

Exclusion Criteria

Another investigational medication within 60 days or 5 half-lives, whichever is longer prior to Day 1

Consumption of caffeine-containing substances within 72 h prior to Day 1 or Check-in

Occupation involving the handling of ETEC, cholera, or Shigella bacteria

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Sentinel dosing group receives VENBETA6890 or placebo, with monitoring for adverse events

2 days

Multiple visits for dosing and monitoring

Treatment Part B

Inpatient cohort receives VENBETA6890 or placebo, followed by ETEC challenge and monitoring

6 days

Inpatient stay with continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 60 days

Treatment Details

Interventions

• VENBETA6890

Trial Overview The trial is testing VENBETA6890, an oral human monoclonal IgA antibody, against a placebo to see if it's safe and can prevent diarrhea when challenged with E. coli bacteria. Up to 36 participants will be randomly assigned to receive either the drug or placebo.

Participant Groups

Group I: Part B Arm 1 Experimental Treatment 1 Intervention

Part B Arm 1 Participants receive Investigational Product

Group II: Part A arm 1 Investigational Product Experimental Treatment 1 Intervention

Arm 1 Investigational product - Venbeta

Group III: Part A Arm 2 Placebo Group 1 Intervention

Part A Arm 2 Placebo

Group IV: Part B Arm 2 Placebo Group 1 Intervention

Part B Arm 2 Particpants receive placebo.

Who Is Running the Clinical Trial?

Mark Klempner

Lead Sponsor

Trials

1

Recruited

40+

Bill and Melinda Gates Foundation

Collaborator

Trials

428

Recruited

23,060,000+

Pharmaron CPC, Inc.

Collaborator

Trials

1

Recruited

40+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Findings from Research

The 5-HT3-receptor antagonist KB-R6933 effectively inhibited diarrhea induced by serotonin (5-HT) in mice, suggesting its potential as a treatment for certain types of diarrhea.

KB-R6933 also reduced intestinal fluid secretion stimulated by cholera toxin in rats, indicating its broader therapeutic potential in managing diarrhea-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the 5-hydroxytryptamine3 (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models. Ozaki, A., Yoshidomi, M., Sukamoto, T.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Effect of the 5-hydroxytryptamine3 (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models. [2022]

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

Efficacy and safety of pinaverium bromide combined with flupentixol-melitracen for diarrhea-type irritable bowel syndrome: A systematic review and meta-analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Role of pinaverium bromide in south Indian patients with irritable bowel syndrome. [2012]

5. Australia pubmed.ncbi.nlm.nih.gov

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome. [2022]