Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)
- Conditions
- Clostridium Difficile Infection (CDI)
- Interventions
- Registration Number
- NCT03244644
- Lead Sponsor
- Rebiotix Inc.
- Brief Summary
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe Clostridioides difficile infection (CDI) resulting in hospitalization within the last year may be eligible for the study. Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.
- Detailed Description
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 as compared to a Placebo in preventing recurrent episodes of CDI and (ii) safety via assessment of adverse events. The primary efficacy analysis of the study will be a Bayesian hierarchical model, which formally incorporates data from a previous randomized Phase 2b study (Protocol 2014-01, NCT02299570) of RBX2660.
Follow-up office visits occur at weeks 1-, 4- and 8 after completing the blinded study treatment. Telephone assessments for adverse events occur during weeks 2, 3 and 6 after the study treatment and at months 3 and 6. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization within the last year may be eligible for the study. Study Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 320
- ≥ 18 years old.
- Medical record documentation of recurrent CDI per the study definition, that includes either: a) at least one recurrence after a primary episode and has completed at least one round of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization within the last year.
- A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.
- Is currently taking or was just prescribed antibiotics to control CDI related diarrhea at the time of enrollment.
[Note: Subject's CDI diarrhea must be controlled (<3 unformed/loose stools/day) while taking this course of antibiotics]
- Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.
- Previous fecal transplant
- History 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.
- Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy)
- An absolute neutrophil count of <1000 cells/µL during screening.
- Pregnant, breastfeeding, or intends to become pregnant during study participation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding Placebo Open label RBX2660 (only for confirmed CDI recurrence) Placebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding RBX2660 RBX2660 RBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant RBX2660 Open label RBX2660 (only for confirmed CDI recurrence) RBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant
- Primary Outcome Measures
Name Time Method Efficacy of RBX2660 Compared to Placebo Through 8 Weeks 8 weeks after completing the study treatment The primary efficacy endpoint was the absence of CDI diarrhea for 8 weeks after study treatment. The model-estimated rate of treatment success, that is the model-estimated percentage of participants that met the primary efficacy endpoint, was estimated using a Bayesian hierarchical model, which formally incorporated data from a previous randomized Phase 2B study (NCT02299570) of RBX2660.
- Secondary Outcome Measures
Name Time Method Sustained Clinical Response Through 6 Months After Blinded Treatment 6 months after completing the study treatment The rates of Sustained Clinical Response (i.e., the occurrence of new CDI infections from baseline through 6 months) was assessed by either the rate of new CDI infections after treatment success at 8 weeks (durability) or the frequency of total CDI infections from baseline through 6 months.
Sustained Clinical Response was compared between the RBX2660 group and the control group using a chi-square test. Patients who exited prior to their 6-month follow-up were conservatively counted as a Treatment Failure
Trial Locations
- Locations (62)
Oxnard
🇺🇸Oxnard, California, United States
West Jordan
🇺🇸West Jordan, Utah, United States
Athens
🇺🇸Athens, Alabama, United States
Shreveport
🇺🇸Shreveport, Louisiana, United States
Marshfield
🇺🇸Marshfield, Wisconsin, United States
Boston
🇺🇸Boston, Massachusetts, United States
Las Vegas
🇺🇸Las Vegas, Nevada, United States
Miami
🇺🇸Miami, Florida, United States
New York
🇺🇸New York, New York, United States
Victoria
🇨🇦Victoria, British Columbia, Canada
Toledo
🇺🇸Toledo, Ohio, United States
Topeka
🇺🇸Topeka, Kansas, United States
Wichita
🇺🇸Wichita, Kansas, United States
Calgary
🇨🇦Calgary, Alberta, Canada
Edmonton
🇨🇦Edmonton, Alberta, Canada
Vancouver
🇨🇦Vancouver, British Columba, Canada
Gurnee
🇺🇸Gurnee, Illinois, United States
Dothan
🇺🇸Dothan, Alabama, United States
Phoenix
🇺🇸Phoenix, Arizona, United States
Lancaster
🇺🇸Lancaster, California, United States
North Little Rock
🇺🇸North Little Rock, Arkansas, United States
Hamden
🇺🇸Hamden, Connecticut, United States
Jacksonville
🇺🇸Jacksonville, Florida, United States
Port Orange
🇺🇸Port Orange, Florida, United States
Idaho Falls
🇺🇸Idaho Falls, Idaho, United States
Atlanta
🇺🇸Atlanta, Georgia, United States
Highland Park
🇺🇸Highland Park, Illinois, United States
Maywood
🇺🇸Maywood, Illinois, United States
Lexington
🇺🇸Lexington, Kentucky, United States
Lafayette
🇺🇸Lafayette, Indiana, United States
Detroit
🇺🇸Detroit, Michigan, United States
Rochester
🇺🇸Rochester, New York, United States
Plymouth
🇺🇸Plymouth, Minnesota, United States
St. Louis
🇺🇸Saint Louis, Missouri, United States
Teaneck
🇺🇸Teaneck, New Jersey, United States
Durham
🇺🇸Durham, North Carolina, United States
North Massapequa
🇺🇸North Massapequa, New York, United States
Greenville
🇺🇸Greenville, North Carolina, United States
Wilmington
🇺🇸Wilmington, North Carolina, United States
Fargo
🇺🇸Fargo, North Dakota, United States
Flourtown
🇺🇸Flourtown, Pennsylvania, United States
Wyomissing
🇺🇸Wyomissing, Pennsylvania, United States
Dallas
🇺🇸Dallas, Texas, United States
Houston
🇺🇸Houston, Texas, United States
Rapid City
🇺🇸Rapid City, South Dakota, United States
Hixson
🇺🇸Hixson, Tennessee, United States
Seattle
🇺🇸Seattle, Washington, United States
Winchester
🇺🇸Winchester, Virginia, United States
Madison
🇺🇸Madison, Wisconsin, United States
Moncton
🇨🇦Moncton, New Brunswick, Canada
Fredericton
🇨🇦Fredericton, New Brunswick, Canada
Uniontown
🇺🇸Uniontown, Pennsylvania, United States
Los Angeles
🇺🇸Los Angeles, California, United States
Springfield
🇺🇸Springfield, Virginia, United States
Sacramento
🇺🇸Sacramento, California, United States
Aurora
🇺🇸Aurora, Colorado, United States
Omaha
🇺🇸Omaha, Nebraska, United States
Portland
🇺🇸Portland, Oregon, United States
New Orleans
🇺🇸New Orleans, Louisiana, United States
Charleston
🇺🇸Charleston, South Carolina, United States
Gainesville
🇺🇸Gainesville, Florida, United States
Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States