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

NCT03788434 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CONSORTIUM (VE303-002)
• Study Type: interventional
• Target: 79
• Locations: 2 countries
• Sites: 37

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).

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• VE303 Strains Detected

  24 weeks

• VE303 Relative Abundance

  24 weeks

Other Outcomes (7)

• CDI Recurrence Week 4

  4 Weeks

• CDI Recurrence Week 12

  12 Weeks

• CDI Recurrence Week 24

  24 Weeks

Study Arms (3)

VE303 High Dose

EXPERIMENTAL

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 Low Dose

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

VE303 DRUG

VE303 is a live biotherapeutic product containing 8 clonal human commensal bacterial strains manufactured under Good Manufacturing Practices (GMP) conditions.

VE303 High Dose; VE303 Low Dose

Placebo DRUG

Placebo capsules contained microcrystalline cellulose and were visually identical to VE303 capsules. Placebo capsules did not contain any VE303 Drug Product.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vedanta Biosciences, Inc.: lead

Study Sites (37)

Phoenix Clinical, LLC

Phoenix, Arizona, 85014, United States

Location

Mayo Clinic, Clinical Studies Unit

Phoenix, Arizona, 85054, United States

Location

NEA Baptist Clinic

Jonesboro, Arkansas, 72401, United States

Location

Alliance Research Institute

Canoga Park, California, 91304, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, 06518, United States

Location

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

Gastro Florida

Clearwater, Florida, 33765, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Guardian Angel Research Center

Tampa, Florida, 33614, United States

Location

Anne Arundel Health System Research Insitute

Annapolis, Maryland, 21401, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Covenant HealthCare

Saginaw, Michigan, 48604, United States

Location

Mayo Clinic

Rochester, Minnesota, 55906, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

Southeastern Research Center

Winston-Salem, North Carolina, 27103, United States

Location

Toledo Institute of Clinical Research Inc

Toledo, Ohio, 43617, United States

Location

TruCare Internal Medicine and Infectious Diseases

DuBois, Pennsylvania, 15801, United States

Location

Frontier Clinical Research, LLC

Uniontown, Pennsylvania, 15401, United States

Location

Advanced Clinical Research-Be Well MD

Cedar Park, Texas, 78613, United States

Location

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

Clinrx Research Joseph INC

Plano, Texas, 75007, United States

Location

Infectious Disease Associates of Central Virginia Infectious Disease

Lynchburg, Virginia, 24501, United States

Location

Seattle Infectious Disease Clinic

Seattle, Washington, 98101, United States

Location

Advanced Clinical Research-Spokane Gastroenterology

Spokane, Washington, 99202, United States

Location

Foothills Medical Centre - Microbial Health Clinic

Calgary, Alberta, T2N2T9, Canada

Location

CARe Clinic

Red Deer, Alberta, T4N6V7, Canada

Location

Moncton Hospital

Moncton, New Brunswick, E1C6Z8, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N4A6, Canada

Location

Viable Clinical Research

Scarborough Village, Ontario, M1P2T7, Canada

Location

Q&T Research Chicoutimi

Chicoutimi, Quebec, G7H7Y8, Canada

Location

CHU de Québec-Université Laval

Québec, Quebec, G1V 4G2, Canada

Location

Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-

Trois-Rivières, Quebec, G8Z3R9, Canada

Location

Related Publications (1)

• Louie T, Golan Y, Khanna S, Bobilev D, Erpelding N, Fratazzi C, Carini M, Menon R, Ruisi M, Norman JM, Faith JJ, Olle B, Li M, Silber JL, Pardi DS. VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA. 2023 Apr 25;329(16):1356-1366. doi: 10.1001/jama.2023.4314.

  PMID: 37060545 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Jeffrey Silber
• Organization: Vedanta Biosciences

ConsortiumIO-ctinquiries@vedantabio.com

(857) 706-1427

Study Officials

• Darrell Pardi, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 27, 2018
• Study Start: February 8, 2019
• Primary Completion: June 2, 2021
• Study Completion: September 15, 2021
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (29); CA (8)