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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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CDI, Clostridium Difficile Infection Recurrence, Clostridium Difficile Infection, Clostridium Difficile, Clostridioides Difficile Infection Recurrence, Clostridioides Difficile Infection, Clostridioides Difficile

Intervention / Treatment
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* Drug: VE303
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Partial Inclusion Criteria: Able and willing to provide written informed consent 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) CDI symptoms must have started within 30 days (inclusive) prior to the day of randomization The diarrhea was considered unlikely to have another etiology. Completed an Investigator's choice SOC antibiotic regimen of a minimum of 10 days and up to 21 days of total duration Have a positive C. difficile stool Recovered from any complications of severe or fulminant CDI and clinically stable by the time of randomization. Partial Exclusion Criteria: 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. Known or suspected toxic megacolon and/or known small bowel ileus at the time of randomization. Contraindication to oral/enteral therapy (e.g., severe reflux, severe nausea/vomiting, or ileus). Prior administration of genetically modified investigational live bacterial/fungal/bacteriophage/viral isolates for CDI-associated diarrhea 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. Use of drugs that alter gut motility History of acute leukemia or hematopoietic stem cell transplantation or myelosuppressive chemotherapy within 2 months prior to randomization. Subjects with compromised immune system 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. History of confirmed celiac disease, inflammatory bowel disease, short gut, gastrointestinal tract fistulas, or ischemia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VE303 High Dose<br>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<br>* VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.<br>|
| Experimental: VE303 Low Dose<br>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<br>* VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.<br>|
| Placebo Comparator: Placebo<br>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<br>* Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium Difficile Infection Recurrence, Clostridium Difficile Infection, Clostridium Difficile, VE303, Consortium, Vedanta, CDI, C. Diff, CDiff, Clostridiodes Difficile Infection Recurrence, Clostridiodes Difficile Infection, Clostridioides Difficile