VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Purpose
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).
Conditions
- Clostridium Difficile
- Clostridium Difficile Infections
- Clostridium Difficile Infection Recurrence
- Clostridioides Difficile Infection
- Clostridioides Difficile Infection Recurrence
- CDI
- C. Diff Infection
- Recurrent Clostridium Difficile Infection
- C.Difficile Diarrhea
- Diarrhea Infectious
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental VE303 |
Subjects assigned to the VE303 arm will take 3 capsules containing VE303 per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode. |
|
|
Placebo Comparator Placebo |
Subjects assigned to the placebo arm will take 3 placebo capsules per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode. |
|
Recruiting Locations
Huntsville, Alabama 35801
Sun City, Arizona 85351
Culver City, California 90230
Los Angeles, California 90027
San Diego, California 92161
Thousand Oaks, California 91360
Torrance, California 90502
Bristol, Connecticut 06010
Hamden, Connecticut 06518
Clearwater, Florida 33756
Fort Lauderdale, Florida 33308
Jacksonville, Florida 32256
Port Orange, Florida 32127
Saint Cloud, Florida 34769
Tampa, Florida 33612
Tampa, Florida 33614
Athens, Georgia 30607
Atlanta, Georgia 30308
Decatur, Georgia 30033
Marietta, Georgia 30060
Idaho Falls, Idaho 83404
Burr Ridge, Illinois 60527
Indianapolis, Indiana 46202
New Albany, Indiana 47150
Kansas City, Kansas 66160
Louisville, Kentucky 40218
New Orleans, Louisiana 70121
Chevy Chase, Maryland 20815
Boston, Massachusetts 02114
Boston, Massachusetts 02115
Ann Arbor, Michigan 48105
Royal Oak, Michigan 48073
Minneapolis, Minnesota 55455
Rochester, Minnesota 55905
St Louis, Missouri 63110
Weldon Spring, Missouri 63304
New Brunswick, New Jersey 08901
Somers Point, New Jersey 08244
Manhasset, New York 11030
New York, New York 10016
New York, New York 10021
Harrisburg, Pennsylvania 17110
Philadelphia, Pennsylvania 19104
Uniontown, Pennsylvania 15401
Charleston, South Carolina 29425
Cordova, Tennessee 38018
Nashville, Tennessee 37232
Dallas, Texas 75246
Richmond, Virginia 23229
Seattle, Washington 98101
Milwaukee, Wisconsin 53207
More Details
- Status
- Recruiting
- Sponsor
- Vedanta Biosciences, Inc.