Clinical trial NCT02299570: Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection
Official title: A Phase 2B Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study Demonstrating the Efficacy and Safety of Rebiotix RBX2660 (Microbiota Suspension) for the Treatment of Recurrent Clostridium Difficile Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Enterocolitis Clostridium Difficile Recurrent
Keywords: Clostridium difficile
C diff
CDI
CDAD
Fecal transplant
Fecal Microbiota Transplant
Diarrhea
FMT
Microbiota restoration therapy
Microbiota suspension
Fecal bacteriotherapy
C diff diarrhea
Lead sponsor: Rebiotix Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-24
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. Patients who have had at least two recurrences of C. difficile infection (CDI) after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.

Detailed description: This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 compared to placebo at 8 weeks and (ii) safety via assessment of adverse events. Study visits are at 1-, 4- and 8-weeks after treatment with additional follow-up at 3, 6 12 and 24 months post treatment. Patients who have had at least two recurrences of C. difficile infection (CDI) after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years
* Medical record documentation of recurrent CDI either: a) at least two recurrences after a primary episode and has completed at least two rounds of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization.
* Documented history that the subject's recurrent CDI is controlled while on antibiotics even if the subject is not currently on antibiotics.
* A positive stool test for the presence of C. difficile within 60 days prior to enrollment.

Exclusion Criteria:

* A known history of continued C. difficile diarrhea while taking on a course of antibiotics prescribed for CDI treatment.
* Requires antibiotic therapy for a condition other than recurrent CDI.
* Previous fecal transplant prior to study enrollment.
* History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
* History of irritable bowel syndrome (IBS).
* History of chronic diarrhea.
* History of celiac disease.
* Colostomy.
* Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
* Life expectancy of \< 12 months.
* Compromised immune system.

Primary outcomes:
measure: Treatment Success of Group A (2 Doses of RBX2660) vs Group B (2 Doses of Placebo) (ITT)
timeFrame: 8 weeks after last assigned study treatment
Secondary outcomes:
measure: Treatment Success Between Group C (1 Enema of RBX2660 and 1 Enema of Placebo) vs Group B (Two Enemas of Placebo) (ITT)
timeFrame: 8-weeks
measure: Treatment Success Evaluated Between Group A (Two Enemas of RBX2660) Versus Group C (1 Enema of RBX2660 and 1 Enema of Placebo) (ITT)
timeFrame: 8-weeks
measure: SF-36 Scores Obtained at the 1-week, 4-week, and 8-week Assessments Visits During the Double-blind Period as Compared to Baseline (ITT)
timeFrame: 8-week
measure: Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group B (ITT)
timeFrame: 8-weeks
measure: Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group C vs. Group B (ITT)
timeFrame: 8-weeks
measure: Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group C (ITT)
timeFrame: 8-weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Idaho Falls
country: United States
facility: Grand Teton Research Group
state: Idaho
city: Chicago
country: United States
facility: Loyola University Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Infectious Diseases of Indiana
state: Indiana
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: New York
country: United States
facility: New York-Presbyterian Hospital/Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: Gastroenterology Group of Rochester
state: New York
city: Fargo
country: United States
facility: Sanford Health
state: North Dakota
city: Cleveland
country: United States
facility: Louis Stokes Cleveland VA Medical Center
state: Ohio
city: Lima
country: United States
facility: Regional Infectious Diseases and Infusion Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Hospital
state: Ontario
Study officials:
affiliation: Wayne State University
name: Teena Chopra, MD MPH
role: STUDY_CHAIR
References:
citation: van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
citation: Moayyedi P, Marshall JK, Yuan Y, Hunt R. Canadian Association of Gastroenterology position statement: fecal microbiota transplant therapy. Can J Gastroenterol Hepatol. 2014 Feb;28(2):66-8. doi: 10.1155/2014/346590. No abstract available.
citation: Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011 Nov;53(10):994-1002. doi: 10.1093/cid/cir632.
citation: Kwak S, Choi J, Hink T, Reske KA, Blount K, Jones C, Bost MH, Sun X, Burnham CD, Dubberke ER, Dantas G; CDC Prevention Epicenter Program. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome. 2020 Aug 31;8(1):125. doi: 10.1186/s40168-020-00907-9.
citation: Dubberke ER, Lee CH, Orenstein R, Khanna S, Hecht G, Gerding DN. Results From a Randomized, Placebo-Controlled Clinical Trial of a RBX2660-A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection. Clin Infect Dis. 2018 Sep 28;67(8):1198-1204. doi: 10.1093/cid/ciy259.