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

• ClinicalTrials.gov Identifier: NCT03788434
• Recruitment Status: Completed
• First Posted: December 27, 2018
• Results First Posted: July 3, 2023
• Last Update Posted: July 3, 2023
• Sponsor: Vedanta Biosciences, Inc.
• Information provided by (Responsible Party): Vedanta Biosciences, Inc.

Tracking Information

• First Submitted Date: December 19, 2018
• First Posted Date: December 27, 2018
• Results First Submitted Date: August 29, 2022
• Results First Posted Date: July 3, 2023
• Last Update Posted Date: July 3, 2023
• Actual Study Start Date: February 8, 2019
• Actual Primary Completion Date: June 2, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2023)

CDI Recurrence Week 8 [ Time Frame: 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).

Original Primary Outcome Measures (submitted: December 21, 2018)

Selection of Phase 3 dose for VE303 [ Time Frame: 24 weeks ]

The primary objective is to determine the recommended VE303 Phase 3 dose regimen based on safety and efficacy, as indicated by the C difficile infection (CDI) recurrence rate.

Current Secondary Outcome Measures (submitted: June 29, 2023)

• VE303 Strains Detected [ Time Frame: 24 weeks ]
  Characterize the number of VE303 strains detected in the fecal microbiome at week 24.
• VE303 Relative Abundance [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: December 21, 2018)

• Characterize VE303 colonization [ Time Frame: 24 weeks ]
  Secondary objective is to characterize VE303 colonization in the fecal microbiome after 14 days of treatment with VE303.
• Characterize Changes in the Fecal Microbiome [ Time Frame: 24 weeks ]
  Secondary objective is to characterize changes in the fecal microbiome after 14 days of treatment with VE303.

Current Other Pre-specified Outcome Measures (submitted: March 16, 2023)

• CDI Recurrence Week 4 [ Time Frame: 4 Weeks ]
  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).
• CDI Recurrence Week 12 [ Time Frame: 12 Weeks ]
  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).
• CDI Recurrence Week 24 [ Time Frame: 24 Weeks ]
  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).
• Microbiota Diversity [ Time Frame: 24 weeks ]
  Characterize the fecal microbiome Shannon Diversity at week 24.
• Determine the Recommended VE303 Phase 3 Dose Regimen(s). [ Time Frame: 31 Months 1 Week ]
  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.
• Changes in the Fecal Metabolomic Profile, Including Short-chain Fatty Acids and Bile Acids. [ Time Frame: 31 Months 1 Week ]
  Changes in the fecal metabolomic profile, including short-chain fatty acids and bile acids for the duration of the study.
• Taxonomic Composition [ Time Frame: 31 Months, 1 Week ]
  Characterize Taxonomic Composition

Original Other Pre-specified Outcome Measures (submitted: December 21, 2018)

• CDI recurrence week 8 [ Time Frame: 8 weeks after first study dose ]
  Proportion of subjects with CDI recurrence before or at Week 8 (i.e., 8 weeks after the first dose of study treatment).
• CDI recurrence week 4 [ Time Frame: 4 weeks after first study dose ]
  Proportion of subjects without CDI recurrence before or at Week 4 (i.e., 4 weeks after the first dose of study treatment)
• CDI recurrence week 12 [ Time Frame: 12 weeks after first study dose ]
  Proportion of subjects without CDI recurrence before or at Week 12 (i.e., 12 weeks after the first dose of study treatment)
• CDI recurrence week 24 [ Time Frame: 24 weeks after first study dose ]
  Proportion of subjects without CDI recurrence before or at Week 24 (i.e., 24 weeks after the first dose of study treatment).
• Microbiota diversity [ Time Frame: 24 weeks ]
  Changes in fecal taxonomic composition after 14 days of blinded treatment with VE303.
• Taxonomic Composition [ Time Frame: 24 weeks ]
  Changes in fecal taxonomic composition after 14 days of blinded treatment with VE303.
• Metabolomic profile [ Time Frame: 24 weeks ]
  Changes in the fecal metabolomic profile, including short chain fatty acids and bile acids after 14 days of blinded treatment with VE303.

Descriptive Information

• Brief Title: Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
• Official Title: CONSORTIUM - A Double-Blind Placebo-Controlled Phase 2 Study of VE303 for Prevention of Recurrent Clostridium (Clostridioides) Difficile Infection
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This Phase 2 study evaluated the safety and efficacy of the study drug, VE303, at preventing subsequent CDI-associated diarrhea compared with placebo, following completion of at least 1 successful course of SOC antibiotics for subjects with pCDI at high risk for recurrence or subjects with rCDI.

Participants in the study were randomized into 3 arms in a 1:1:1 ratio of high dose VE303, low dose VE303, and placebo.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

To reduce potential bias and increase study data integrity, study participants, care providers, site investigators, and study outcomes assessors were masked to study treatment assignment.

Primary Purpose: Prevention

Condition

• Clostridium Difficile Infection Recurrence
• Clostridium Difficile Infection
• Clostridium Difficile
• Clostridioides Difficile Infection Recurrence
• Clostridioides Difficile Infection
• Clostridioides Difficile
• CDI

Intervention

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

Study Arms

• 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.
  Intervention: Drug: VE303
• 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.
  Intervention: Drug: VE303
• 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.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 28, 2021): 79
• Original Estimated Enrollment (submitted: December 21, 2018): 146
• Actual Study Completion Date: September 15, 2021
• Actual Primary Completion Date: June 2, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03788434
• Other Study ID Numbers: CONSORTIUM (VE303-002)
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Vedanta Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Vedanta Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Darrell Pardi, MD; Mayo Clinic

• PRS Account: Vedanta Biosciences, Inc.
• Verification Date: June 2023