Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection (CONSORTIUM)

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

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).

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection; Clostridium Difficile Infection Recurrence; Clostridium Difficile; CDI; Clostridioides Difficile Infection; Clostridioides Difficile; Clostridioides Difficile Infection Recurrence
• Intervention / Treatment: Drug: VE303; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N2T9
      • Foothills Medical Centre - Microbial Health Clinic
    • Red Deer, Alberta, Canada, T4N6V7
      • Care Clinic
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C6Z8
      • Moncton Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N4A6
      • St. Joseph's Healthcare Hamilton
    • Scarborough, Ontario, Canada, M1P2T7
      • Viable Clinical Research
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H7Y8
      • Q&T Research Chicoutimi
    • Quebec City, Quebec, Canada, G1V 4G2
      • CHU de Quebec-Universite Laval
    • Trois-Rivières, Quebec, Canada, G8Z3R9
      • Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Phoenix Clinical, LLC
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic, Clinical Studies Unit
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • California
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • Ventura, California, United States, 93003
      • Ventura Clinical Trials
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida
    • Clearwater, Florida, United States, 33765
      • Gastro Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33614
      • Guardian Angel Research Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Health System Research Insitute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Saginaw, Michigan, United States, 48604
      • Covenant HealthCare
  • Minnesota
    • Rochester, Minnesota, United States, 55906
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Toledo, Ohio, United States, 43617
      • Toledo Institute of Clinical Research Inc
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • TruCare Internal Medicine and Infectious Diseases
    • Uniontown, Pennsylvania, United States, 15401
      • Frontier Clinical Research, LLC
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Advanced Clinical Research-Be Well MD
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates
    • Plano, Texas, United States, 75007
      • ClinRx Research Joseph INC
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Infectious Disease Associates of Central Virginia Infectious Disease
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Infectious Disease Clinic
    • Spokane, Washington, United States, 99202
      • Advanced Clinical Research-Spokane Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: VE303; VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.
Experimental: 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.	Drug: VE303; VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.
Placebo Comparator: Placebo; Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.	Drug: Placebo; Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
VE303 Strains Detected	Characterize the number of VE303 strains detected in the fecal microbiome at week 24.	24 weeks
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Microbiota Diversity	Characterize the fecal microbiome Shannon Diversity at week 24.	24 weeks
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
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
Taxonomic Composition	Characterize Taxonomic Composition	31 Months, 1 Week

Collaborators and Investigators

• Sponsor: Vedanta Biosciences, Inc.
• Investigators: Principal Investigator: Darrell Pardi, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2019
• Primary Completion (Actual): June 2, 2021
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Clostridium Difficile; CDI; Clostridium Difficile Infection; Clostridium Difficile Infection Recurrence; VE303; Consortium; Vedanta; C. Diff; CDiff; Clostridiodes Difficile Infection; Clostridiodes Difficile Infection Recurrence; Clostridioides Difficile
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Clostridium Infections
• Other Study ID Numbers: CONSORTIUM (VE303-002)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No