Microbiota Restoration Therapy for Recurrent Clostridium Difficile-associated Diarrhea

NCT ID: NCT01925417

Last Updated: 2019-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-07-31

Brief Summary

This study will assess the safety of a new biologic drug, RBX2660 (microbiota suspension) as a treatment for recurrent Clostridium difficile-associated diarrhea (CDAD), which is the primary symptom of recurrent Clostridium difficile infection. All eligible subjects will receive RBX2660.

Detailed Description

This is the first study of a microbiota suspension derived from intestinal microbes. The primary assessments for this open label, multi-center study are (i) occurrence of product-related adverse events and (ii) resolution of CDAD at 56 days after administration of RBX2660. Subjects will also be assessed for time to CDAD recurrence, quality of life changes, and number of hospitalizations and length of stay for recurrent CDAD. Study visits will be at 7, 30, and 60 days after RBX2660 administration with additional follow-up at 3 and 6 months post treatment. Patients who have had at least two recurrences of CDAD 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 CDAD resulting in hospitalization may be eligible for the study.

Conditions

Recurrent Clostridium Difficile Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RBX2660 (microbiota suspension)

enema-based delivery of RBX2660

Group Type: EXPERIMENTAL

RBX2660 (microbiota suspension)

Intervention Type: BIOLOGICAL

Interventions

RBX2660 (microbiota suspension)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years
• Medical record documentation of CDAD either: a) at least two recurrences after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or b) have had at least two episodes of severe CDAD resulting in hospitalization.
• Willing and able to have an enema(s).
• Already taking or will start a course of oral antibiotics for CDAD symptoms for 10-14 days, including at least seven days of oral vancomycin.
• Willing and able to complete the required subject diary.

Exclusion Criteria

• Continued (uncontrolled) CDAD after completing a 10-14 day course of oral antibiotics.
• Requires antibiotic therapy for a condition other than CDAD.
• 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.
• History of cirrhosis of the liver or ascites.
• Disease symptoms caused by a confirmed intestinal pathogen other than Clostridium difficile.
• Has a colostomy.
• Intraabdominal surgery within the last 60 days.
• Evidence of active, severe colitis.
• History of short gut syndrome or motility disorders.
• Requires the regular use of medications that affect bowel motility (e.g., metoclopramide, narcotics, loperamide).
• Planned therapy in the next 3 months that may cause diarrhea (e.g., chemotherapy).
• Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
• Life expectancy of < 12 months.
• Compromised immune system, e.g., HIV infection (any CD4 count); AIDS-defining diagnosis or CD4 <200/mm3; inherited/primary immune disorders; immunodeficient or immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy; or current or recent (< 90 days) treatment with immunosuppressant medications.
• Taking steroids (≥ 20 mg a day) or is expected to be on steroids for more than 30 days after enrollment.
• Neutropenia (white blood cell count <1000 cells/µL).

• 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

Dimitri Drekonja, MD

Role: STUDY_CHAIR

Veteran Administration Medical Center

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Denver Health and University of Colorado

Denver, Colorado, United States

Borland-Groover Clinic

Jacksonville, Florida, United States

Edward Hines Jr VA Hospital (veterans only)

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Ochsner Clinic

New Orleans, Louisiana, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Detroit Medical Center

Detroit, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Mayo Clinic - Minnesota

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Sanford Research/USD

Fargo, North Dakota, United States

Countries

United States

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)

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)

Rohlke F, Stollman N. Fecal microbiota transplantation in relapsing Clostridium difficile infection. Therap Adv Gastroenterol. 2012 Nov;5(6):403-20. doi: 10.1177/1756283X12453637.

Reference Type: BACKGROUND

PMID: 23152734 (View on PubMed)

Langdon A, Schwartz DJ, Bulow C, Sun X, Hink T, Reske KA, Jones C, Burnham CD, Dubberke ER, Dantas G; CDC Prevention Epicenter Program. Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study. Genome Med. 2021 Feb 16;13(1):28. doi: 10.1186/s13073-021-00843-9.

Reference Type: DERIVED

PMID: 33593430 (View on PubMed)

Orenstein R, Dubberke E, Hardi R, Ray A, Mullane K, Pardi DS, Ramesh MS; PUNCH CD Investigators. Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study. Clin Infect Dis. 2016 Mar 1;62(5):596-602. doi: 10.1093/cid/civ938. Epub 2015 Nov 12.

Reference Type: DERIVED

PMID: 26565008 (View on PubMed)

Other Identifiers

2013-001

Identifier Type: -

Identifier Source: org_study_id