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

Phase 2

Completed

• Conditions: Clostridium Difficile Infection Recurrence; Clostridioides Difficile Infection Recurrence; Clostridioides Difficile Infection; Clostridium Difficile Infection; Clostridioides Difficile; CDI; Clostridium Difficile
• Interventions: Drug: Placebo; Drug: VE303

• Registration Number: NCT03788434
• Lead Sponsor: Vedanta Biosciences, Inc.

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.

Study Timeline

• Study First Submitted: 2018-12-19
• Study First Submitted QC: 2018-12-21
• Study First Posted: 2018-12-27
• Study Start: 2019-02-08
• Primary Completion: 2021-06-02
• Study Completion: 2021-09-15
• Results First Submitted: 2022-08-29
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-29
• Last Update Submitted: 2023-06-29
• Results First Posted: 2023-07-03
• Last Update Posted: 2023-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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.

Partial

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.
VE303 High Dose	VE303	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.
VE303 Low Dose	VE303	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.

Primary Outcome Measures

Name	Time	Method
CDI Recurrence Week 8	8 weeks	Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 8 (i.e., 8 weeks after the first dose of study treatment).

Secondary Outcome Measures

Name	Time	Method
VE303 Strains Detected	24 weeks	Characterize the number of VE303 strains detected in the fecal microbiome at week 24.
VE303 Relative Abundance	24 weeks	Proportion of VE303 strains is defined as the abundance proportion of all 8 VE303 strains relative to the total microbial composition of the sample.

Trial Locations

Locations (37)

Innovative Research of West Florida; 🇺🇸 Clearwater, Florida, United States

Gastro Florida; 🇺🇸 Clearwater, Florida, United States

Moncton Hospital; 🇨🇦 Moncton, New Brunswick, Canada

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Seattle Infectious Disease Clinic; 🇺🇸 Seattle, Washington, United States

NEA Baptist Clinic; 🇺🇸 Jonesboro, Arkansas, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Medical Research Center of Connecticut, LLC; 🇺🇸 Hamden, Connecticut, United States

Covenant HealthCare; 🇺🇸 Saginaw, Michigan, United States

Anne Arundel Health System Research Insitute; 🇺🇸 Annapolis, Maryland, United States

Phoenix Clinical, LLC; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic, Clinical Studies Unit; 🇺🇸 Phoenix, Arizona, United States

Guardian Angel Research Center; 🇺🇸 Tampa, Florida, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of California, Davis Medical Center; 🇺🇸 Sacramento, California, United States

Southeastern Research Center; 🇺🇸 Winston-Salem, North Carolina, United States

Alliance Research Institute; 🇺🇸 Canoga Park, California, United States

Ventura Clinical Trials; 🇺🇸 Ventura, California, United States

Clinical Research of Gastonia; 🇺🇸 Gastonia, North Carolina, United States

New York University Langone Medical Center; 🇺🇸 New York, New York, United States

Toledo Institute of Clinical Research Inc; 🇺🇸 Toledo, Ohio, United States

TruCare Internal Medicine and Infectious Diseases; 🇺🇸 DuBois, Pennsylvania, United States

Texas Centers for Infectious Disease Associates; 🇺🇸 Fort Worth, Texas, United States

Frontier Clinical Research, LLC; 🇺🇸 Uniontown, Pennsylvania, United States

Advanced Clinical Research-Be Well MD; 🇺🇸 Cedar Park, Texas, United States

Infectious Disease Associates of Central Virginia Infectious Disease; 🇺🇸 Lynchburg, Virginia, United States

Clinrx Research Joseph INC; 🇺🇸 Plano, Texas, 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

Viable Clinical Research; 🇨🇦 Scarborough, Ontario, Canada

Q&T Research Chicoutimi; 🇨🇦 Chicoutimi, Quebec, Canada

CHU de Québec-Université Laval; 🇨🇦 Quebec City, Quebec, Canada

Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-; 🇨🇦 Trois-Rivières, Quebec, Canada

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada