Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Biological: RBX2660
* Drug: Standard of Care Antibiotics


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI, Clostridium difficile, C diff, CDAD, Fecal transplant, Fecal Microbiota transplant, diarrhea, FMT, microbiota restoration therapy, microbiota suspension, fecal bacteriotherapy, C diff diarrhea