Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Condition: Clostridium Difficile Infection Recurrence; Clostridium Difficile Infection; Clostridium Difficile; Clostridioides Difficile Infection Recurrence; Clostridioides Difficile Infection; Clostridioides Difficile; CDI
MeSH terms: Infections; Communicable Diseases; Clostridium Infections; Recurrence
Intervention: VE303; Placebo
Intervention description: VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.; Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
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.
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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).
    

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.