VE303: VE303 is a live biotherapeutic product (LBP) consisting of 8 clonally derived, nonpathogenic, nontoxigenic, commensal bacteria strains manufactured under Good Manufacturing Practices (GMP) conditions.
Placebo: Placebo capsules contain microcrystalline cellulose. Placebo capsules are visually identical to and not discernible from VE303 capsules. Placebo capsules will not contain any VE303 drug product.
Study summary
The overall objective of the RESTORATiVE303 study is to evaluate the safety and the Clostridioides difficile infection (CDI) recurrence rate at Week 8 in participants who receive a 14-day course of VE303 or matching placebo. The objectives and endpoints are identical for Stage 1 (recurrent CDI) and Stage 2 (high-risk primary CDI).
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria (For enrollment in Stage 1: recurrent CDI population):
* Age ≥ 12 years where permitted, and ≥ 18 years in other locations, with a laboratory-confirmed qualifying episode of CDI and at least 1 prior occurrence within the last 6 months
Key Inclusion Criteria (For enrollment in Stage 2: primary CDI with high-risk for recurrence population):
* Age ≥ 75 years with a laboratory-confirmed qualifying episode of CDI
* OR age ≥ 12 years where permitted, and ≥ 18 years in other locations, with least two of the following risk factors:
1. Age ≥ 65 years
2. Kidney dysfunction, defined as estimated creatinine clearance \< 60 mL/min/1.73 m\^2 at the time of the qualifying CDI episode
3. History of regular use of a proton pump inhibitor (PPI) within the past 2 months and expectation of continued use of PPIs throughout the study
4. History of a prior CDI episode between 6 and 12 months prior to enrollment
5. Immunosuppression due to an underlying disease or its treatment
6. Has undergone solid organ or hematopoietic stem cell transplantation
Key Inclusion Criteria (For enrollment in Stage 1 or 2):
* The qualifying episode of CDI must meet all the following criteria:
1. New onset of ≥ 3 unformed bowel movements (ie, Types 5 to 7 on the Bristol stool scale) within 24 hours for 2 consecutive days
2. CDI symptoms started within 4 weeks prior to initiation of standard of care (SoC) antibiotic therapy for CDI
3. Stool sample collected before (or no later than 72 hours after) initiation of SoC antibiotic therapy that was positive in a CDI laboratory test, defined as enzyme immunoassay (EIA) for toxin A/B and glutamate dehydrogenase (GDH) with polymerase chain reaction (PCR) reflex testing for discordant EIA/GDH results, performed at either a local laboratory or the central laboratory
4. Diarrhea considered unlikely to have another etiology
* Prior to receiving any study medication, the participant should:
1. Receive and complete a course of SoC antibiotic therapy for at least 10 days, up to a maximum of 28 days (Note: choice of agent is at the physician's discretion and antibiotic tapering is not allowed). It is permissible for decentralized participants to be randomized during SoC antibiotic administration.
2. Meet the criterion of a successful clinical response, defined attaining symptomatic control of the qualifying CDI episode, ie, \< 3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days
* Able to receive the first dose of study drug on the last planned day of SoC antibiotic administration for a qualifying CDI episode, or no later than 2 days after completion of antibiotic dosing
* Recovered from any complications of severe or fulminant CDI and be clinically stable by the time of randomization
Key Exclusion Criteria (For both Stage 1 and Stage 2):
* History of chronic diarrhea (defined as ≥ 3 loose stools per day lasting for at least 4 weeks) within 3 months prior to randomization that is not related to CDI
* Known or suspected toxic megacolon or small bowel ileus at the time of randomization
* History of confirmed celiac disease, inflammatory bowel disease, microscopic colitis, short gut, GI tract fistulas, or a recent episode (within 6 months of screening) of intestinal ischemia or ischemic colitis
* Receipt of bezlotoxumab during the course of SoC antibiotic treatment for the qualifying CDI episode
* Use of antidiarrheal drugs (eg, loperamide, diphenoxylate) within 3 days prior to the planned first dose of study drug
* Anticipated administration of oral or parenteral antibacterial therapy for a non-CDI indication after randomization through Week 24 (end of study)
* Probiotics, whether characterized as a dietary/food supplement, or a drug, are prohibited within 2 days before starting study drug and through the dosing period. (Note: consumption of food-based products such as yogurt, kombucha, and kefir are permitted.)
* Absolute neutrophil count (ANC) of \< 0.5 ×10\^9 cells/L on 2 consecutive occasions within 7 days prior to randomization, or sustained ANC \< 1.0 × 10\^9 cells/L
Primary outcome measure(s)
CDI Recurrence Rate at Week 8 — 8 weeks Proportion of participants with laboratory-confirmed CDI recurrence before or at Week 8.
Trial sites (215)
Facility
City
Region
Status
Metro Infectious Disease Consultants
Huntsville
Alabama
Recruiting
Advanced Gastroenterology, P.C.
Chandler
Arizona
Withdrawn
Mayo Clinic Hospital
Phoenix
Arizona
Withdrawn
GI Alliance
Sun City
Arizona
Recruiting
Om Research, LLC
Apple Valley
California
Withdrawn
Science 37 Inc (Remote/Home option)
Culver City
California
Recruiting
Children's Hospital of Los Angeles
Los Angeles
California
Recruiting
VA San Diego Healthcare System
San Diego
California
Recruiting
North America Research Institute
San Dimas
California
Withdrawn
Clinical Trials Management Services
Thousand Oaks
California
Recruiting
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance
California
Recruiting
Connecticut Clinical Research Institute
Bristol
Connecticut
Recruiting
Medical Research Center of Connecticut
Hamden
Connecticut
Recruiting
Hartford Hospital
Hartford
Connecticut
Withdrawn
Gastro Florida
Clearwater
Florida
Recruiting
Proactive Clinical Research, LLC
Fort Lauderdale
Florida
Recruiting
Encore Borland-Groover Clinical Research
Jacksonville
Florida
Recruiting
GI Pros Research
Naples
Florida
Recruiting
Advanced Medical Research Center
Port Orange
Florida
Recruiting
KM International Research Operation LLC
Saint Cloud
Florida
Recruiting
James A. Haley Veterans' Hospital
Tampa
Florida
Recruiting
International Center for Research
Tampa
Florida
Recruiting
Summit Clinical Research, LLC
Athens
Georgia
Recruiting
Emory University Hospital Midtown
Atlanta
Georgia
Recruiting
Metro Infectious Disease Consultants
Decatur
Georgia
Recruiting
Regional Infectious Diseases and Infusion Center, Inc.
La Grange
Georgia
Withdrawn
Gastrointestinal Specialists of Georgia
Marietta
Georgia
Recruiting
Snake River Research, PLLC
Idaho Falls
Idaho
Recruiting
Metro Infectious Disease Consultants
Burr Ridge
Illinois
Recruiting
NorthShore University Health System - Evanston Hospital
Evanston
Illinois
Withdrawn
GI Alliance
Gurnee
Illinois
Recruiting
Innovative Clinical Research Center, LLC (ICRC)
Island Lake
Illinois
Withdrawn
Indiana University Health University Hospital
Indianapolis
Indiana
Recruiting
Gastroenterology Health Partners
New Albany
Indiana
Recruiting
Deaconess GI Specialty Center
Newburgh
Indiana
Withdrawn
University of Kansas Medical Center
Kansas City
Kansas
Recruiting
IDC Clinical Research, LLC
Wichita
Kansas
Withdrawn
Gastroenterology Health Partners
Louisville
Kentucky
Recruiting
Ochsner Clinic Foundation
New Orleans
Louisiana
Recruiting
Johns Hopkins Hospital
Baltimore
Maryland
Active Not Recruiting
+ 175 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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