Back to resultsPhase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection (CONSORTIUM)
Primary Purpose
Clostridium Difficile Infection Recurrence, Clostridium Difficile Infection, Clostridium Difficile
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VE303
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Clostridium Difficile Infection Recurrence focused on measuring 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
Eligibility Criteria
Partial Inclusion Criteria:
- Able and willing to provide written informed consent
- Subjects with a qualifying CDI episode who have a prior history of CDI diarrhea or first occurrence of CDI diarrhea with a higher risk for recurrence (≥ 65 years of age)
- CDI symptoms must have started within 30 days (inclusive) prior to the day of randomization
- The diarrhea is considered unlikely to have another etiology.
- Complete 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 is 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.
Sites / Locations
- Phoenix Clinical, LLC
- Mayo Clinic, Clinical Studies Unit
- NEA Baptist Clinic
- Alliance Research Institute
- University of California, Davis Medical Center
- Ventura Clinical Trials
- Medical Research Center of Connecticut, LLC
- Innovative Research of West Florida
- Gastro Florida
- University of Florida
- Guardian Angel Research Center
- Anne Arundel Health System Research Insitute
- Tufts Medical Center
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Covenant HealthCare
- Mayo Clinic
- New York University Langone Medical Center
- Clinical Research of Gastonia
- Southeastern Research Center
- Toledo Institute of Clinical Research Inc
- TruCare Internal Medicine and Infectious Diseases
- Frontier Clinical Research, LLC
- Advanced Clinical Research-Be Well MD
- Texas Centers for Infectious Disease Associates
- Clinrx Research Joseph INC
- Infectious Disease Associates of Central Virginia Infectious Disease
- Seattle Infectious Disease Clinic
- Advanced Clinical Research-Spokane Gastroenterology
- Foothills Medical Centre - Microbial Health Clinic
- CARe Clinic
- Moncton Hospital
- St. Joseph's Healthcare Hamilton
- Viable Clinical Research
- Q&T Research Chicoutimi
- CHU de Québec-Université Laval
- Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
VE303 High Dose
VE303 Low Dose
Placebo
Arm Description
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.
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.
Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
VE303 Strains Detected
Characterize the number of VE303 strains detected in the fecal microbiome at week 24.
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.
Full Information
NCT ID
NCT03788434
First Posted
December 19, 2018
Last Updated
June 29, 2023
Sponsor
Vedanta Biosciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03788434
Brief Title
Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Acronym
CONSORTIUM
Official Title
CONSORTIUM - A Double-Blind Placebo-Controlled Phase 2 Study of VE303 for Prevention of Recurrent Clostridium (Clostridioides) Difficile Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 8, 2019 (Actual)
Primary Completion Date
June 2, 2021 (Actual)
Study Completion Date
September 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vedanta Biosciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
79 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VE303 High Dose
Arm Type
Experimental
Arm Description
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.
Arm Title
VE303 Low Dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.
Intervention Type
Drug
Intervention Name(s)
VE303
Intervention Description
VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.
Primary Outcome Measure Information:
Title
CDI Recurrence Week 8
Description
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).
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
VE303 Strains Detected
Description
Characterize the number of VE303 strains detected in the fecal microbiome at week 24.
Time Frame
24 weeks
Title
VE303 Relative Abundance
Description
Proportion of VE303 strains is defined as the abundance proportion of all 8 VE303 strains relative to the total microbial composition of the sample.
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
CDI Recurrence Week 4
Description
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).
Time Frame
4 Weeks
Title
CDI Recurrence Week 12
Description
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).
Time Frame
12 Weeks
Title
CDI Recurrence Week 24
Description
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).
Time Frame
24 Weeks
Title
Microbiota Diversity
Description
Characterize the fecal microbiome Shannon Diversity at week 24.
Time Frame
24 weeks
Title
Determine the Recommended VE303 Phase 3 Dose Regimen(s).
Description
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.
Time Frame
31 Months 1 Week
Title
Changes in the Fecal Metabolomic Profile, Including Short-chain Fatty Acids and Bile Acids.
Description
Changes in the fecal metabolomic profile, including short-chain fatty acids and bile acids for the duration of the study.
Time Frame
31 Months 1 Week
Title
Taxonomic Composition
Description
Characterize Taxonomic Composition
Time Frame
31 Months, 1 Week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Darrell Pardi, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phoenix Clinical, LLC
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85014
Country
United States
Facility Name
Mayo Clinic, Clinical Studies Unit
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
NEA Baptist Clinic
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
Facility Name
Alliance Research Institute
City
Canoga Park
State/Province
California
ZIP/Postal Code
91304
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Ventura Clinical Trials
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
Medical Research Center of Connecticut, LLC
City
Hamden
State/Province
Connecticut
ZIP/Postal Code
06518
Country
United States
Facility Name
Innovative Research of West Florida
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Gastro Florida
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Guardian Angel Research Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Anne Arundel Health System Research Insitute
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Covenant HealthCare
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48604
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55906
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Clinical Research of Gastonia
City
Gastonia
State/Province
North Carolina
ZIP/Postal Code
28054
Country
United States
Facility Name
Southeastern Research Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Toledo Institute of Clinical Research Inc
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
TruCare Internal Medicine and Infectious Diseases
City
DuBois
State/Province
Pennsylvania
ZIP/Postal Code
15801
Country
United States
Facility Name
Frontier Clinical Research, LLC
City
Uniontown
State/Province
Pennsylvania
ZIP/Postal Code
15401
Country
United States
Facility Name
Advanced Clinical Research-Be Well MD
City
Cedar Park
State/Province
Texas
ZIP/Postal Code
78613
Country
United States
Facility Name
Texas Centers for Infectious Disease Associates
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Clinrx Research Joseph INC
City
Plano
State/Province
Texas
ZIP/Postal Code
75007
Country
United States
Facility Name
Infectious Disease Associates of Central Virginia Infectious Disease
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24501
Country
United States
Facility Name
Seattle Infectious Disease Clinic
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Advanced Clinical Research-Spokane Gastroenterology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Foothills Medical Centre - Microbial Health Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N2T9
Country
Canada
Facility Name
CARe Clinic
City
Red Deer
State/Province
Alberta
ZIP/Postal Code
T4N6V7
Country
Canada
Facility Name
Moncton Hospital
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C6Z8
Country
Canada
Facility Name
St. Joseph's Healthcare Hamilton
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N4A6
Country
Canada
Facility Name
Viable Clinical Research
City
Scarborough
State/Province
Ontario
ZIP/Postal Code
M1P2T7
Country
Canada
Facility Name
Q&T Research Chicoutimi
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H7Y8
Country
Canada
Facility Name
CHU de Québec-Université Laval
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
Facility Name
Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-
City
Trois-Rivières
State/Province
Quebec
ZIP/Postal Code
G8Z3R9
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
We'll reach out to this number within 24 hrs