Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

NCT02299570 | Completed Phase 2 Results DMC

• 1 other identifier: 2014-01
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 21

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.

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

Outcome Measures

Primary Outcomes (1)

• Treatment Success of Group A (2 Doses of RBX2660) vs Group B (2 Doses of Placebo) (ITT)

  The primary endpoint is to evaluate treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema, of Group A (two enemas of RBX2660) vs. Group B (two enemas of placebo).

  8 weeks after last assigned study treatment

Secondary Outcomes (6)

• Treatment Success Between Group C (1 Enema of RBX2660 and 1 Enema of Placebo) vs Group B (Two Enemas of Placebo) (ITT)

  8-weeks

• Treatment Success Evaluated Between Group A (Two Enemas of RBX2660) Versus Group C (1 Enema of RBX2660 and 1 Enema of Placebo) (ITT)

  8-weeks

• 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)

  8-week

• Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group B (ITT)

  8-weeks

• Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group C vs. Group B (ITT)

  8-weeks

Study Arms (3)

Group A

ACTIVE COMPARATOR

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

Biological: RBX2660 (microbiota suspension)

Group B

PLACEBO COMPARATOR

Two enemas of placebo administered 7 days apart

Other: Placebo

Group C

ACTIVE COMPARATOR

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

Biological: RBX2660 (microbiota suspension); Other: Placebo

Interventions

RBX2660 (microbiota suspension) BIOLOGICAL

A suspension of intestinal microbes

Group A; Group C

Placebo OTHER

A suspension of saline and cryoprotectant

Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rebiotix Inc.: lead

Study Sites (21)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Borland-Groover Clinic

Jacksonville, Florida, 32256, United States

Location

Grand Teton Research Group

Idaho Falls, Idaho, 83404, United States

Location

Loyola University Chicago

Chicago, Illinois, 60153, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Infectious Diseases of Indiana

Indianapolis, Indiana, 46260, United States

Location

Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Hospital Queens

Flushing, New York, 11355, United States

Location

New York-Presbyterian Hospital/Weill Cornell Medical College

New York, New York, 10065, United States

Location

Gastroenterology Group of Rochester

Rochester, New York, 14618, United States

Location

Sanford Health

Fargo, North Dakota, 58122, United States

Location

Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, 44106, United States

Location

Regional Infectious Diseases and Infusion Center

Lima, Ohio, 45801, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

St. Joseph's Hospital

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (7)

• 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.

  PMID: 23323867 BACKGROUND

• 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.

  PMID: 25232572 BACKGROUND

• 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.

  PMID: 22002980 BACKGROUND

• Lee C, Feuerstadt P, Louie T, Bancke L, Guthmueller B, Harvey A, Hoeyer F, Orenstein R, Dubberke ER, Khanna S. Integrated analysis of the safety of fecal microbiota, live-jslm in adults with recurrent Clostridioides difficile infection from five prospective clinical trials: an update. Therap Adv Gastroenterol. 2025 Nov 12;18:17562848251395566. doi: 10.1177/17562848251395566. eCollection 2025.

  PMID: 41245385 DERIVED

• 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.

  PMID: 36544075 DERIVED

• 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.

  PMID: 32862830 DERIVED

• 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.

  PMID: 29617739 DERIVED

Related Links

• Sponsor website

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Assoc. Director of Clinical Research
• Organization: Rebiotix

Sarah.Mische@Ferring.com

651-705-8778

Study Officials

• Teena Chopra, MD MPH

  Wayne State University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 24, 2014
• Study Start: December 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2018
• Last Updated: January 15, 2021
• Results First Posted: July 27, 2018

Record last verified: 2020-12

Locations

CA (2); US (19)