Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

Phase 2

Completed

• Conditions: Clostridium Difficile Infection
• Interventions: Biological: RBX2660; Drug: Standard of Care Antibiotics

• Registration Number: NCT02589847
• Lead Sponsor: Rebiotix Inc.

Brief Summary

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).

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 Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-10-26
• Study First Submitted QC: 2015-10-27
• Study First Posted: 2015-10-28
• Primary Completion: 2017-06
• Study Completion: 2019-03
• Results First Submitted: 2020-04-28
• Results First Submitted QC: 2020-04-28
• Results First Posted: 2020-05-11
• Status Verified: 2021-02
• Last Update Submitted: 2021-03-25
• Last Update Posted: 2021-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 272

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RBX2660 Open-label	RBX2660	RBX2660 (microbiota suspension)
Historical control antibiotics	Standard of Care Antibiotics	Retrospective Historical Control with standard of care

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks	8 weeks after treatment	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.

Secondary Outcome Measures

Name	Time	Method
Quality of Life (SF-36)	8-Weeks	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.
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months	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.