Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

An Open-label Efficacy and Safety Assessment of Rebiotix RBX2660 (Microbiota Suspension) for the Treatment of Recurrent Clostridium Difficile Infection

This study will evaluate efficacy and safety information about RBX2660 for the treatment of recurrent Clostridium difficile infection (CDI), and will compare the efficacy of one treatment with RBX2660 versus antibiotic-treated historical controls. Enrolled subjects will receive one treatment consisting of two doses of RBX2660 (microbiota suspension).

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Biological: RBX2660; Drug: Standard of Care Antibiotics

Detailed Description

This is a prospective, multicenter, open-label study assessing the efficacy and safety of RBX2660 as an adjunct to antibiotics for the treatment of recurrent CDI. Efficacy of RBX2660, measured by the recurrence-free rate of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment with RBX2660, will be evaluated by comparing the recurrence-free rate observed in the study population to the recurrence-free rate identified from antibiotic-treated historical controls.

Patients who have had either a) at least two recurrences after a primary episode (i.e., at least three episodes) and have completed at least two rounds of standard-of-care oral antibiotics or b) have had at least two episodes of severe CDI resulting in hospitalization may be eligible to participate in the study. Study visits are 1- and 8-weeks after treatment with additional follow-up assessments at 3,6,12, and 24 months post treatment.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
  • Ontario
    • Hamilton, Ontario, Canada, L8N4A6
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
  • California
    • Sacramento, California, United States, 95817
  • Florida
    • Bay Pines, Florida, United States, 33744
    • Coral Springs, Florida, United States, 33065
    • Gainesville, Florida, United States, 32610
    • Miami, Florida, United States, 33101
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Maywood, Illinois, United States, 60153
  • Indiana
    • Indianapolis, Indiana, United States, 46260
    • Lafayette, Indiana, United States, 47904
  • Kentucky
    • Lexington, Kentucky, United States, 40506
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Minnesota
    • Rochester, Minnesota, United States, 55905
    • Saint Paul, Minnesota, United States, 55130
  • Missouri
    • Saint Louis, Missouri, United States, 63110
  • Nebraska
    • Omaha, Nebraska, United States, 68198
  • New York
    • Bronx, New York, United States, 10468
    • Flushing, New York, United States, 11355
    • Rochester, New York, United States, 14618
    • Syracuse, New York, United States, 52325
  • North Dakota
    • Fargo, North Dakota, United States, 58122
  • Ohio
    • Lima, Ohio, United States, 45801
  • Tennessee
    • Jackson, Tennessee, United States, 38305
  • Texas
    • Houston, Texas, United States, 77025
  • Virginia
    • Springfield, Virginia, United States, 22150
    • Virginia Beach, Virginia, United States, 23454

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years old.
• Medical record documentation of recurrent CDI including a positive C. difficile test within 60 days prior to enrollment and 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 CDI diarrhea despite being on a course of antibiotics prescribed for CDI treatment.
• Requires continuous antibiotic therapy for a condition other than CDI.
• Previous successful (resolution of CDI diarrhea) fecal transplant for recurrent CDI < 6 months prior to study enrollment.
• Previous unsuccessful (recurrent CDI diarrhea was unresolved) fecal transplant.
• Previous treatment with RBX2660.
• Diagnosis of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
• Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.
• History of chronic diarrhea.
• History of celiac disease.
• Disease symptoms caused by a confirmed intestinal pathogen other than C. difficile.
• Colostomy.
• Planned surgery requiring perioperative antibiotics within 3 months of study enrollment.
• Life expectancy of < 12 months.
• Compromised immune system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RBX2660 Open-label; RBX2660 (microbiota suspension)	Biological: RBX2660; suspension of intestinal microbes
Other: Historical control antibiotics; Retrospective Historical Control with standard of care	Drug: Standard of Care Antibiotics; Standard of Care Antibiotics; Other Names: Antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks	Participants were evaluated 8 weeks after study treatment to assess efficacy of RBX2660. Efficacy was assessed as the absence of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment.	8 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (SF-36)	The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH [All abbreviations are defined in table]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment.	Baseline
Quality of Life (SF-36)	The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH [All abbreviations are defined in table]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment.	8-Weeks
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months	Major complications of rCDI, defined as death, septic shock, toxic megacolon, colonic perforation, emergency colectomy, or ICU admission) were collected and reported as a safety-related endpoint.	24 months

Collaborators and Investigators

• Sponsor: Rebiotix Inc.
• Investigators: Study Chair: Arnab Ray, MD, Ochsner Health System

Publications and helpful links

General Publications

• Orenstein R, Dubberke ER, Khanna S, Lee CH, Yoho D, Johnson S, Hecht G, DuPont HL, Gerding DN, Blount KF, Mische S, Harvey A. Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial. BMC Infect Dis. 2022 Mar 12;22(1):245. doi: 10.1186/s12879-022-07256-y.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: October 26, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimate): October 28, 2015

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: diarrhea; Clostridium difficile; FMT; CDI; Fecal transplant; CDAD; C diff; microbiota suspension; Fecal Microbiota transplant; microbiota restoration therapy; fecal bacteriotherapy; C diff diarrhea
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 2015-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No