Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection

NCT ID: NCT03788434

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-08
• Study Completion Date: 2021-09-15

Brief Summary

This study evaluated the safety and efficacy of VE303 for participants with primary C. difficile infection (pCDI) at high risk for recurrence or subjects with recurrent C. difficile infections (rCDI).

Detailed Description

CONSORTIUM was a randomized, placebo-controlled double-blind Phase 2 study to evaluate safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of VE303 in prevention of subsequent Clostridioides difficile infection (CDI) -associated diarrhea compared with placebo following completion of at least 1 successful course of standard-of-care (SOC) antibiotics. VE303 or placebo capsules were taken orally for 14 days after completion of a course of SOC antibiotics. The proportions of subjects experiencing a confirmed CDI recurrence within 8 weeks after the first dose of study treatment were compared across the study arms, to understand the efficacy of VE303 in preventing rCDI.

The study originally planned to enroll 146 subjects but through a protocol amendment was revised to an enrollment target of 60 to 80 subjects with a prior history of CDI diarrhea or first occurrence of CDI diarrhea with a higher risk for recurrence. Subjects must have had a positive C. difficile stool sample and have responded to SOC antibiotic treatment.

Conditions

Clostridium Difficile Infection Recurrence; Clostridium Difficile Infection; Clostridium Difficile; Clostridioides Difficile Infection Recurrence; Clostridioides Difficile Infection; Clostridioides Difficile; CDI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

VE303 High Dose

Study subjects assigned the high dose VE303 arm took 10 capsules (dosage: 8.0 × 10\^9 CFU daily) containing VE303 per day for 14 days.

Group Type: EXPERIMENTAL

VE303

Intervention Type: DRUG

VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.

VE303 Low Dose

Study subjects assigned to the low dose VE303 arm took 2 capsules (dosage: 1.6 × 10\^9 CFU daily) containing VE303 per day for 14 days.

Group Type: EXPERIMENTAL

VE303

Intervention Type: DRUG

VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.

Placebo

Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.

Interventions

VE303

VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.

Intervention Type: DRUG

Placebo

Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Able and willing to provide written informed consent

2. Subjects with a qualifying CDI episode who had a prior history of CDI diarrhea (≥ 18 years of age) or first occurrence of CDI diarrhea with a higher risk for recurrence (≥ 75 years of age, or ≥ 65 years of age with one or more prespecified conditions)

3. CDI symptoms must have started within 30 days (inclusive) prior to the day of randomization

4. The diarrhea was considered unlikely to have another etiology.

5. Completed an Investigator's choice SOC antibiotic regimen of a minimum of 10 days and up to 21 days of total duration

6. Have a positive C. difficile stool

7. Recovered from any complications of severe or fulminant CDI and clinically stable by the time of randomization.

Exclusion Criteria

1. History of diarrhea (defined as 3 or more loose stools per day lasting for at least 4 weeks) that was not related to C. difficile infection within the 3 months prior to randomization.

2. Known or suspected toxic megacolon and/or known small bowel ileus at the time of randomization.

3. Contraindication to oral/enteral therapy (e.g., severe reflux, severe nausea/vomiting, or ileus).

4. Prior administration of genetically modified investigational live bacterial/fungal/bacteriophage/viral isolates for CDI-associated diarrhea

5. History of administration of fecally-derived investigational live biotherapeutic products, or fecally-derived live bacterial isolates for CDI-associated diarrhea including fecal microbiota transplantation (FMT) within the last 6 months.

6. Use of drugs that alter gut motility

7. History of acute leukemia or hematopoietic stem cell transplantation or myelosuppressive chemotherapy within 2 months prior to randomization.

8. Subjects with compromised immune system

9. Major gastrointestinal surgery (e.g., significant bowel resection or diversion) within 3 months prior to randomization or any history of total colectomy or bariatric surgery that disrupts the gastrointestinal lumen.

10. History of confirmed celiac disease, inflammatory bowel disease, short gut, gastrointestinal tract fistulas, or ischemia.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vedanta Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrell Pardi, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Phoenix Clinical, LLC

Phoenix, Arizona, United States

Mayo Clinic, Clinical Studies Unit

Phoenix, Arizona, United States

NEA Baptist Clinic

Jonesboro, Arkansas, United States

Alliance Research Institute

Canoga Park, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

Ventura Clinical Trials

Ventura, California, United States

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States

Innovative Research of West Florida

Clearwater, Florida, United States

Gastro Florida

Clearwater, Florida, United States

University of Florida

Gainesville, Florida, United States

Guardian Angel Research Center

Tampa, Florida, United States

Anne Arundel Health System Research Insitute

Annapolis, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Covenant HealthCare

Saginaw, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

New York University Langone Medical Center

New York, New York, United States

Clinical Research of Gastonia

Gastonia, North Carolina, United States

Southeastern Research Center

Winston-Salem, North Carolina, United States

Toledo Institute of Clinical Research Inc

Toledo, Ohio, United States

TruCare Internal Medicine and Infectious Diseases

DuBois, Pennsylvania, United States

Frontier Clinical Research, LLC

Uniontown, Pennsylvania, United States

Advanced Clinical Research-Be Well MD

Cedar Park, Texas, United States

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, United States

Clinrx Research Joseph INC

Plano, Texas, United States

Infectious Disease Associates of Central Virginia Infectious Disease

Lynchburg, Virginia, United States

Seattle Infectious Disease Clinic

Seattle, Washington, United States

Advanced Clinical Research-Spokane Gastroenterology

Spokane, Washington, United States

Foothills Medical Centre - Microbial Health Clinic

Calgary, Alberta, Canada

CARe Clinic

Red Deer, Alberta, Canada

Moncton Hospital

Moncton, New Brunswick, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Viable Clinical Research

Scarborough Village, Ontario, Canada

Q&T Research Chicoutimi

Chicoutimi, Quebec, Canada

CHU de Québec-Université Laval

Québec, Quebec, Canada

Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-

Trois-Rivières, Quebec, Canada

Countries

United States; Canada

References

Louie T, Golan Y, Khanna S, Bobilev D, Erpelding N, Fratazzi C, Carini M, Menon R, Ruisi M, Norman JM, Faith JJ, Olle B, Li M, Silber JL, Pardi DS. VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA. 2023 Apr 25;329(16):1356-1366. doi: 10.1001/jama.2023.4314.

Reference Type: DERIVED

PMID: 37060545 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CONSORTIUM (VE303-002)

Identifier Type: -

Identifier Source: org_study_id