Recruiting NCT06237452

VE303 for Prevention of Recurrent Clostridioides Difficile Infection

Phase III Interventional Clostridium Difficile Clostridium Difficile Infections Clostridium Difficile Infection Recurrence Clostridioides Difficile Infection

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: VE303, Placebo.
Who it may be relevant to: Registry conditions: Clostridium Difficile, Clostridium Difficile Infections, Clostridium Difficile Infection Recurrence, Clostridioides Difficile Infection. Basic parameters: from 12 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Belgium, Brazil, Bulgaria +19
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection

Overview

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).

Interventions

Biological 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.
Biological 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.

Primary outcome measures

CDI Recurrence Rate at Week 8 [Time frame: 8 weeks]

Eligibility criteria

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:

Age ≥ 65 years
Kidney dysfunction, defined as estimated creatinine clearance < 60 mL/min/1.73 m\^2 at the time of the qualifying CDI episode
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
History of a prior CDI episode between 6 and 12 months prior to enrollment
Immunosuppression due to an underlying disease or its treatment
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:

New onset of ≥ 3 unformed bowel movements (ie, Types 5 to 7 on the Bristol stool scale) within 24 hours for 2 consecutive days
CDI symptoms started within 4 weeks prior to initiation of standard of care (SoC) antibiotic therapy for CDI
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
Diarrhea considered unlikely to have another etiology
Prior to receiving any study medication, the participant should:

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.
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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Prevention