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

Clostridium Difficile Infection Clinical Trial

— CONSORTIUM  

Official title:

CONSORTIUM - A Double-Blind Placebo-Controlled Phase 2 Study of VE303 for Prevention of Recurrent Clostridium (Clostridioides) Difficile Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03788434
• Other study ID #: CONSORTIUM (VE303-002)
• Status: Completed
• Phase: Phase 2
• Start date: February 8, 2019
• Est. completion date: September 15, 2021

Study information

• Verified date: June 2023
• Source: Vedanta Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: September 15, 2021
• Est. primary completion date: June 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Partial 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 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.

Related Conditions & MeSH terms

• CDI
• Clostridioides Difficile Infection
• Clostridium Difficile
• Clostridium Difficile Infection
• Clostridium Difficile Infection Recurrence
• Clostridium Infections
• Communicable Diseases
• Infections
• Recurrence

Intervention

Drug:
• VE303
VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.
• Placebo
Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre - Microbial Health Clinic	Calgary	Alberta
Canada	Q&T Research Chicoutimi	Chicoutimi	Quebec
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	CHU de Québec-Université Laval	Quebec City	Quebec
Canada	CARe Clinic	Red Deer	Alberta
Canada	Viable Clinical Research	Scarborough	Ontario
Canada	Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-	Trois-Rivières	Quebec
United States	Anne Arundel Health System Research Insitute	Annapolis	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Alliance Research Institute	Canoga Park	California
United States	Advanced Clinical Research-Be Well MD	Cedar Park	Texas
United States	Gastro Florida	Clearwater	Florida
United States	Innovative Research of West Florida	Clearwater	Florida
United States	TruCare Internal Medicine and Infectious Diseases	DuBois	Pennsylvania
United States	Texas Centers for Infectious Disease Associates	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	Infectious Disease Associates of Central Virginia Infectious Disease	Lynchburg	Virginia
United States	New York University Langone Medical Center	New York	New York
United States	Mayo Clinic, Clinical Studies Unit	Phoenix	Arizona
United States	Phoenix Clinical, LLC	Phoenix	Arizona
United States	Clinrx Research Joseph INC	Plano	Texas
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Davis Medical Center	Sacramento	California
United States	Covenant HealthCare	Saginaw	Michigan
United States	Seattle Infectious Disease Clinic	Seattle	Washington
United States	Advanced Clinical Research-Spokane Gastroenterology	Spokane	Washington
United States	Guardian Angel Research Center	Tampa	Florida
United States	Toledo Institute of Clinical Research Inc	Toledo	Ohio
United States	Frontier Clinical Research, LLC	Uniontown	Pennsylvania
United States	Ventura Clinical Trials	Ventura	California
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Vedanta Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CDI Recurrence Week 4	Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 4 (i.e., 4 weeks after the first dose of study treatment).	4 Weeks
Other	CDI Recurrence Week 12	Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 12 (i.e., 12 weeks after the first dose of study treatment).	12 Weeks
Other	CDI Recurrence Week 24	Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 24 (i.e., 24 weeks after the first dose of study treatment).	24 Weeks
Other	Microbiota Diversity	Characterize the fecal microbiome Shannon Diversity at week 24.	24 weeks
Other	Determine the Recommended VE303 Phase 3 Dose Regimen(s).	Determine the recommended VE303 phase 3 dose regimen(s) based on safety and efficacy, as indicated by the CDI recurrence rate for the duration of the study.	31 Months 1 Week
Other	Changes in the Fecal Metabolomic Profile, Including Short-chain Fatty Acids and Bile Acids.	Changes in the fecal metabolomic profile, including short-chain fatty acids and bile acids for the duration of the study.	31 Months 1 Week
Other	Taxonomic Composition	Characterize Taxonomic Composition	31 Months, 1 Week
Primary	CDI Recurrence Week 8	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).	8 weeks
Secondary	VE303 Strains Detected	Characterize the number of VE303 strains detected in the fecal microbiome at week 24.	24 weeks
Secondary	VE303 Relative Abundance	Proportion of VE303 strains is defined as the abundance proportion of all 8 VE303 strains relative to the total microbial composition of the sample.	24 weeks