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
Apple Valley 5324363, California 5332921 92307
Culver City 5341114, California 5332921 90230
Los Angeles 5368361, California 5332921 90027
San Diego 5391811, California 5332921 92161
San Dimas 5391891, California 5332921 91773
Thousand Oaks 5402405, California 5332921 91360
Torrance 5403022, California 5332921 90502
Hamden 4835654, Connecticut 4831725 06518
Clearwater 4151316, Florida 4155751 33756
Fort Lauderdale 4155966, Florida 4155751 33308
Jacksonville 4160021, Florida 4155751 32256
Naples 4165565, Florida 4155751 34102
Port Orange 4169156, Florida 4155751 32127
Saint Cloud 4170965, Florida 4155751 34769
Tampa 4174757, Florida 4155751 33612
Tampa 4174757, Florida 4155751 33614
Athens 4180386, Georgia 4197000 30607
Atlanta 4180439, Georgia 4197000 30308
Decatur 4191124, Georgia 4197000 30033
La Grange 4204230, Georgia 4197000 30240
Marietta 4207783, Georgia 4197000 30060
Idaho Falls 5596475, Idaho 5596512 83404
Burr Ridge 4886090, Illinois 4896861 60527
Evanston 4891382, Illinois 4896861 60201
Island Lake 4897579, Illinois 4896861 60042
Indianapolis 4259418, Indiana 4921868 46202
Newburgh 4262171, Indiana 4921868 47630
Kansas City 4273837, Kansas 4273857 66160
New Orleans 4335045, Louisiana 4331987 70121
Baltimore 4347778, Maryland 4361885 21287
Chevy Chase 4351335, Maryland 4361885 20815
Boston 4930956, Massachusetts 6254926 02111
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02115
Ann Arbor 4984247, Michigan 5001836 48105
Detroit 4990729, Michigan 5001836 48202
Royal Oak 5007804, Michigan 5001836 48073
Minneapolis 5037649, Minnesota 5037779 55455
Rochester 5043473, Minnesota 5037779 55905
Columbia 4381982, Missouri 4398678 65212
St Louis 4407066, Missouri 4398678 63110
Weldon Spring 4413926, Missouri 4398678 63304
New Brunswick 5101717, New Jersey 5101760 08901
Somers Point 4504186, New Jersey 5101760 08244
Manhasset 5125766, New York 5128638 11030
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10021
New York 5128581, New York 5128638 10279
Toledo 5174035, Ohio 5165418 43617
Oklahoma City 4544349, Oklahoma 4544379 73104
Harrisburg 5192726, Pennsylvania 6254927 17110
Philadelphia 4560349, Pennsylvania 6254927 19104
Sayre 5211037, Pennsylvania 6254927 18840
Uniontown 4561859, Pennsylvania 6254927 15401
Charleston 4574324, South Carolina 4597040 29401
Charleston 4574324, South Carolina 4597040 29401
Charleston 4574324, South Carolina 4597040 29414
Charleston 4574324, South Carolina 4597040 29425
Nashville 4644585, Tennessee 4662168 37232
Dallas 4684888, Texas 4736286 75246
Sugar Land 4734825, Texas 4736286 77478
Seattle 5809844, Washington 5815135 98101
More Details
- NCT ID
- NCT06237452
- Status
- Recruiting
- Sponsor
- Vedanta Biosciences, Inc.