VE303 for Prevention of Recurrent Clostridioides Difficile Infection

Clostridium Difficile Clinical Trial

— RESTORATiVE303  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06237452
• Other study ID #: VE303-003
• Status: Recruiting
• Phase: Phase 3
• Start date: May 20, 2024
• Est. completion date: October 2027

Study information

• Verified date: June 2024
• Source: Vedanta Biosciences, Inc.
• Contact: Mary Garfield
• Phone: 857-706-1427
• Email: Consortium02-ctinquiries[@]vedantabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 852
• Est. completion date: October 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria (For enrollment in Stage 1: recurrent CDI population):

• Age = 12 years with a laboratory-confirmed qualifying episode of CDI and at least one prior occurrence of CDI 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 with laboratory-confirmed qualifying episode of CDI and at 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 21 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 1 day 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

• Laboratory-confirmed infectious diarrhea other than CDI (including bacterial, viral, or parasitic etiology) within 30 days prior to randomization

• 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

• Receipt of SER-109/VOWST™, RBX2660/REBYOTA®, or any other approved or investigational genetically modified live bacterial, fungal, viral, or bacteriophage isolates, fecal-derived live bacterial isolates, or other LBPs for CDI-associated diarrhea, including fecal microbiota transplantation, within 6 months prior to randomization

• 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

Related Conditions & MeSH terms

• C.Difficile Diarrhea
• CDI
• Clostridioides Difficile Infection
• Clostridium Difficile
• Clostridium Difficile Infection Recurrence
• Clostridium Difficile Infections
• Clostridium Infections
• Communicable Diseases
• Diarrhea
• Diarrhea Infectious
• Dysentery
• Infections
• Recurrence
• Recurrent Clostridium Difficile Infection

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Summit Clinical Research, LLC	Athens	Georgia
United States	Metro Infectious Disease Consultants	Burr Ridge	Illinois
United States	Advanced Gastroenterology, P.C.	Chandler	Arizona
United States	Lowcountry Infectious Diseases, P.A.	Charleston	South Carolina
United States	Gastro Florida	Clearwater	Florida
United States	Science 37 Inc	Culver City	California
United States	Metro Infectious Disease Consultants	Decatur	Georgia
United States	Proactive Clinical Research, LLC	Fort Lauderdale	Florida
United States	Medical Research Center of Connecticut	Hamden	Connecticut
United States	Susquehanna Research Group - Gastroenterology	Harrisburg	Pennsylvania
United States	Innovative Clinical Research Center, LLC (ICRC)	Island Lake	Illinois
United States	Encore Borland-Groover Clinical Research	Jacksonville	Florida
United States	BioStar Clinical Research	Katy	Texas
United States	Regional Infectious Diseases and Infusion Center, Inc.	LaGrange	Georgia
United States	GI Pros Research	Naples	Florida
United States	Manhattan Clinical Research, LLC	New York	New York
United States	Advanced Medical Research Center	Port Orange	Florida
United States	KM International Research Operation LLC	Saint Cloud	Florida
United States	North America Research Institute	San Dimas	California
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Delta Gastroenterology and Endoscopy Center	Southaven	Mississippi
United States	International Center for Research	Tampa	Florida
United States	Clinical Trials Management Services	Thousand Oaks	California
United States	Toledo Institute of Clinical Research	Toledo	Ohio
United States	Frontier Clinical Research	Uniontown	Pennsylvania
United States	St. Charles Clinical Research	Weldon Spring	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Vedanta Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CDI Recurrence Rate at Week 8	Proportion of participants with laboratory-confirmed CDI recurrence before or at Week 8.	8 weeks