Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

NCT ID: NCT02299570

Last Updated: 2021-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2018-01-31

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.

Conditions

Enterocolitis Clostridium Difficile Recurrent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A

Two enemas of RBX2660 (microbiota suspension) administered 7 days apart

Group Type: ACTIVE_COMPARATOR

RBX2660 (microbiota suspension)

Intervention Type: BIOLOGICAL

A suspension of intestinal microbes

Group B

Two enemas of placebo administered 7 days apart

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

A suspension of saline and cryoprotectant

Group C

1 enema of RBX2660 (microbiota suspension) and 1 enema of placebo administered 7 days apart

Group Type: ACTIVE_COMPARATOR

RBX2660 (microbiota suspension)

Intervention Type: BIOLOGICAL

A suspension of intestinal microbes

Placebo

Intervention Type: OTHER

A suspension of saline and cryoprotectant

Interventions

RBX2660 (microbiota suspension)

A suspension of intestinal microbes

Intervention Type: BIOLOGICAL

Placebo

A suspension of saline and cryoprotectant

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rebiotix Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teena Chopra, MD MPH

Role: STUDY_CHAIR

Wayne State University

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

University of Colorado

Aurora, Colorado, United States

Borland-Groover Clinic

Jacksonville, Florida, United States

Grand Teton Research Group

Idaho Falls, Idaho, United States

Loyola University Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Infectious Diseases of Indiana

Indianapolis, Indiana, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Mayo Clinic Minnesota

Rochester, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

New York Hospital Queens

Flushing, New York, United States

New York-Presbyterian Hospital/Weill Cornell Medical College

New York, New York, United States

Gastroenterology Group of Rochester

Rochester, New York, United States

Sanford Health

Fargo, North Dakota, United States

Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, United States

Regional Infectious Diseases and Infusion Center

Lima, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of British Columbia

Vancouver, British Columbia, Canada

St. Joseph's Hospital

Hamilton, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 23323867 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25232572 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22002980 (View on PubMed)

Dubberke ER, Orenstein R, Khanna S, Guthmueller B, Lee C. Final Results from a Phase 2b Randomized, Placebo-Controlled Clinical Trial of RBX2660: A Microbiota-Based Drug for the Prevention of Recurrent Clostridioides difficile Infection. Infect Dis Ther. 2023 Feb;12(2):703-709. doi: 10.1007/s40121-022-00744-3. Epub 2022 Dec 21.

Reference Type: DERIVED

PMID: 36544075 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32862830 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29617739 (View on PubMed)

Related Links

http://www.rebiotix.com

Sponsor website

Other Identifiers

2014-01

Identifier Type: -

Identifier Source: org_study_id