Phase 2 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection (CONSORTIUM)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| 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.
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Clostridium Difficile Infection Recurrence Clostridium Difficile Infection Clostridium Difficile Clostridioides Difficile Infection Recurrence Clostridioides Difficile Infection Clostridioides Difficile CDI | Drug: VE303 Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 79 participants |
| 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 |
| Official Title: | CONSORTIUM - A Double-Blind Placebo-Controlled Phase 2 Study of VE303 for Prevention of Recurrent Clostridium (Clostridioides) Difficile Infection |
| Actual Study Start Date : | February 8, 2019 |
| Actual Primary Completion Date : | June 2, 2021 |
| Actual Study Completion Date : | September 15, 2021 |
| Arm | Intervention/treatment |
|---|---|
|
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.
|
Drug: VE303
VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions. |
|
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.
|
Drug: VE303
VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions. |
|
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.
|
Drug: Placebo
Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product. |
Primary Outcome Measures :
- 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).
Secondary Outcome Measures :
- 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.
Other Outcome Measures:
- 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
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788434
Locations
Show 37 study locations
Sponsors and Collaborators
Vedanta Biosciences, Inc.
Investigators
| Principal Investigator: | Darrell Pardi, MD | Mayo Clinic |
Study Documents (Full-Text)
Documents provided by Vedanta Biosciences, Inc.:
Documents provided by Vedanta Biosciences, Inc.:
Study Protocol [PDF] July 15, 2021
Statistical Analysis Plan [PDF] July 15, 2021
| Responsible Party: | Vedanta Biosciences, Inc. |
| ClinicalTrials.gov Identifier: | NCT03788434 |
| Other Study ID Numbers: |
CONSORTIUM (VE303-002) |
| First Posted: | December 27, 2018 Key Record Dates |
| Results First Posted: | July 3, 2023 |
| Last Update Posted: | July 3, 2023 |
| Last Verified: | June 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Vedanta Biosciences, Inc.:
|
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 |
Additional relevant MeSH terms:
|
Infections Communicable Diseases Clostridium Infections Recurrence Disease Attributes |
Pathologic Processes Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |