Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

Clostridium Difficile Infection (CDI) Clinical Trial

Official title:

A Phase 3 Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of RBX2660 (Microbiota Suspension) for the Prevention of Clostridium Difficile Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03244644
• Other study ID #: 2017-01
• Status: Completed
• Phase: Phase 3
• Start date: July 31, 2017
• Est. completion date: August 3, 2020

Study information

• Verified date: July 2023
• Source: Rebiotix Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe Clostridioides difficile infection (CDI) resulting in hospitalization within the last year may be eligible for the study. Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.

Description:

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 as compared to a Placebo in preventing recurrent episodes of CDI and (ii) safety via assessment of adverse events. The primary efficacy analysis of the study will be a Bayesian hierarchical model, which formally incorporates data from a previous randomized Phase 2b study (Protocol 2014-01, NCT02299570) of RBX2660.

Follow-up office visits occur at weeks 1-, 4- and 8 after completing the blinded study treatment. Telephone assessments for adverse events occur during weeks 2, 3 and 6 after the study treatment and at months 3 and 6. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization within the last year may be eligible for the study. Study Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: August 3, 2020
• Est. primary completion date: April 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. = 18 years old.

2. Medical record documentation of recurrent CDI per the study definition, that includes either: a) at least one recurrence after a primary episode and has completed at least one round of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization within the last year.

3. A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.

4. Is currently taking or was just prescribed antibiotics to control CDI related diarrhea at the time of enrollment.

[Note: Subject's CDI diarrhea must be controlled (<3 unformed/loose stools/day) while taking this course of antibiotics]

Exclusion Criteria:

1. Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.

2. Previous fecal transplant

3. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.

4. Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.

5. Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy)

6. An absolute neutrophil count of <1000 cells/µL during screening.

7. Pregnant, breastfeeding, or intends to become pregnant during study participation.

Related Conditions & MeSH terms

• Clostridium Difficile Infection (CDI)
• Clostridium Infections
• Communicable Diseases
• Infections

Intervention

Drug:
• RBX2660
RBX2660 is a rectally administered microbiota suspension
• Placebo
Placebo is normal saline solution administered rectally
• Open label RBX2660 (only for confirmed CDI recurrence)
RBX2660 administered as a second treatment after confirmed CDI recurrence following the initial dose of placebo or RBX2660

Locations

Country	Name	City	State
Canada	Calgary	Calgary	Alberta
Canada	Edmonton	Edmonton	Alberta
Canada	Fredericton	Fredericton	New Brunswick
Canada	Moncton	Moncton	New Brunswick
Canada	Vancouver	Vancouver	British Columba
Canada	Victoria	Victoria	British Columbia
United States	Athens	Athens	Alabama
United States	Atlanta	Atlanta	Georgia
United States	Atlanta	Atlanta	Georgia
United States	Aurora	Aurora	Colorado
United States	Boston	Boston	Massachusetts
United States	Charleston	Charleston	South Carolina
United States	Dallas	Dallas	Texas
United States	Detroit	Detroit	Michigan
United States	Dothan	Dothan	Alabama
United States	Durham	Durham	North Carolina
United States	Fargo	Fargo	North Dakota
United States	Flourtown	Flourtown	Pennsylvania
United States	Gainesville	Gainesville	Florida
United States	Greenville	Greenville	North Carolina
United States	Gurnee	Gurnee	Illinois
United States	Hamden	Hamden	Connecticut
United States	Highland Park	Highland Park	Illinois
United States	Hixson	Hixson	Tennessee
United States	Houston	Houston	Texas
United States	Idaho Falls	Idaho Falls	Idaho
United States	Jacksonville	Jacksonville	Florida
United States	Lafayette	Lafayette	Indiana
United States	Lancaster	Lancaster	California
United States	Las Vegas	Las Vegas	Nevada
United States	Lexington	Lexington	Kentucky
United States	Los Angeles	Los Angeles	California
United States	Madison	Madison	Wisconsin
United States	Marshfield	Marshfield	Wisconsin
United States	Maywood	Maywood	Illinois
United States	Miami	Miami	Florida
United States	New Orleans	New Orleans	Louisiana
United States	New York	New York	New York
United States	North Little Rock	North Little Rock	Arkansas
United States	North Massapequa	North Massapequa	New York
United States	Omaha	Omaha	Nebraska
United States	Omaha	Omaha	Nebraska
United States	Oxnard	Oxnard	California
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix	Phoenix	Arizona
United States	Plymouth	Plymouth	Minnesota
United States	Port Orange	Port Orange	Florida
United States	Portland	Portland	Oregon
United States	Rapid City	Rapid City	South Dakota
United States	Rochester	Rochester	Minnesota
United States	Rochester	Rochester	New York
United States	Sacramento	Sacramento	California
United States	St. Louis	Saint Louis	Missouri
United States	Seattle	Seattle	Washington
United States	Shreveport	Shreveport	Louisiana
United States	Springfield	Springfield	Virginia
United States	Teaneck	Teaneck	New Jersey
United States	Toledo	Toledo	Ohio
United States	Topeka	Topeka	Kansas
United States	Uniontown	Uniontown	Pennsylvania
United States	West Jordan	West Jordan	Utah
United States	Wichita	Wichita	Kansas
United States	Wilmington	Wilmington	North Carolina
United States	Winchester	Winchester	Virginia
United States	Wyomissing	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Rebiotix Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Bakken JS. Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations. Microb Ecol Health Dis. 2015 May 29;26:27657. doi: 10.3402/mehd.v26.27657. eCollection 2015. No abstract available. — View Citation

EISEMAN B, SILEN W, BASCOM GS, KAUVAR AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958 Nov;44(5):854-9. No abstract available. — View Citation

Miller MA, Louie T, Mullane K, Weiss K, Lentnek A, Golan Y, Kean Y, Sears P. Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect Dis. 2013 Mar 25;13:148. doi: 10.1186/1471-2334-13-148. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of RBX2660 Compared to Placebo Through 8 Weeks	The primary efficacy endpoint was the absence of CDI diarrhea for 8 weeks after study treatment. The model-estimated rate of treatment success, that is the model-estimated percentage of participants that met the primary efficacy endpoint, was estimated using a Bayesian hierarchical model, which formally incorporated data from a previous randomized Phase 2B study (NCT02299570) of RBX2660.	8 weeks after completing the study treatment
Secondary	Sustained Clinical Response Through 6 Months After Blinded Treatment	The rates of Sustained Clinical Response (i.e., the occurrence of new CDI infections from baseline through 6 months) was assessed by either the rate of new CDI infections after treatment success at 8 weeks (durability) or the frequency of total CDI infections from baseline through 6 months.; Sustained Clinical Response was compared between the RBX2660 group and the control group using a chi-square test. Patients who exited prior to their 6-month follow-up were conservatively counted as a Treatment Failure	6 months after completing the study treatment

External Links

•   Centers for Disease Control page last reviewed March 15, 2021; accessed March 01, 2022.
•   Rebyota sponsor briefing book
•   Sponsor website