Clinical trial NCT03788434: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile Infection Recurrence
Clostridium Difficile Infection
Clostridium Difficile
Clostridioides Difficile Infection Recurrence
Clostridioides Difficile Infection
Clostridioides Difficile
CDI
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
Lead sponsor: Vedanta Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2018-12-27
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: CDI Recurrence Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: VE303 Strains Detected
timeFrame: 24 weeks
measure: VE303 Relative Abundance
timeFrame: 24 weeks
Other outcomes:
measure: CDI Recurrence Week 4
timeFrame: 4 Weeks
measure: CDI Recurrence Week 12
timeFrame: 12 Weeks
measure: CDI Recurrence Week 24
timeFrame: 24 Weeks
measure: Microbiota Diversity
timeFrame: 24 weeks
measure: Determine the Recommended VE303 Phase 3 Dose Regimen(s).
timeFrame: 31 Months 1 Week
measure: Changes in the Fecal Metabolomic Profile, Including Short-chain Fatty Acids and Bile Acids.
timeFrame: 31 Months 1 Week
measure: Taxonomic Composition
timeFrame: 31 Months, 1 Week
Locations:
city: Phoenix
country: United States
facility: Phoenix Clinical, LLC
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic, Clinical Studies Unit
state: Arizona
city: Jonesboro
country: United States
facility: NEA Baptist Clinic
state: Arkansas
city: Canoga Park
country: United States
facility: Alliance Research Institute
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Clearwater
country: United States
facility: Gastro Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Annapolis
country: United States
facility: Anne Arundel Health System Research Insitute
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saginaw
country: United States
facility: Covenant HealthCare
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research Inc
state: Ohio
city: DuBois
country: United States
facility: TruCare Internal Medicine and Infectious Diseases
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Cedar Park
country: United States
facility: Advanced Clinical Research-Be Well MD
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: Plano
country: United States
facility: Clinrx Research Joseph INC
state: Texas
city: Lynchburg
country: United States
facility: Infectious Disease Associates of Central Virginia Infectious Disease
state: Virginia
city: Seattle
country: United States
facility: Seattle Infectious Disease Clinic
state: Washington
city: Spokane
country: United States
facility: Advanced Clinical Research-Spokane Gastroenterology
state: Washington
city: Calgary
country: Canada
facility: Foothills Medical Centre - Microbial Health Clinic
state: Alberta
city: Red Deer
country: Canada
facility: CARe Clinic
state: Alberta
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Scarborough
country: Canada
facility: Viable Clinical Research
state: Ontario
city: Chicoutimi
country: Canada
facility: Q&T Research Chicoutimi
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Québec-Université Laval
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-
state: Quebec
Study officials:
affiliation: Mayo Clinic
name: Darrell Pardi, MD
role: PRINCIPAL_INVESTIGATOR
References: