Back to resultsMicrobiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD2)
Primary Purpose
Enterocolitis Clostridium Difficile Recurrent
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RBX2660 (microbiota suspension)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Enterocolitis Clostridium Difficile Recurrent focused on measuring Clostridium difficile, C diff, CDI, CDAD, Fecal transplant, Fecal Microbiota Transplant, Diarrhea, FMT, Microbiota restoration therapy, Microbiota suspension, Fecal bacteriotherapy, C diff diarrhea
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years
- Medical record documentation of recurrent CDI 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 C. difficile diarrhea while taking on a course of antibiotics prescribed for CDI treatment.
- Requires antibiotic therapy for a condition other than recurrent CDI.
- 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.
- Colostomy.
- Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
- Life expectancy of < 12 months.
- Compromised immune system.
Sites / Locations
- Mayo Clinic Arizona
- University of Colorado
- Borland-Groover Clinic
- Grand Teton Research Group
- Loyola University Chicago
- University of Chicago
- Infectious Diseases of Indiana
- Chevy Chase Clinical Research
- Henry Ford Health System
- Mayo Clinic Minnesota
- Regions Hospital
- Washington University School of Medicine
- New York Hospital Queens
- New York-Presbyterian Hospital/Weill Cornell Medical College
- Gastroenterology Group of Rochester
- Sanford Health
- Louis Stokes Cleveland VA Medical Center
- Regional Infectious Diseases and Infusion Center
- Hospital of the University of Pennsylvania
- University of British Columbia
- St. Joseph's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Arm Label
Group A
Group B
Group C
Arm Description
Two enemas of RBX2660 (microbiota suspension) administered 7 days apart
Two enemas of placebo administered 7 days apart
1 enema of RBX2660 (microbiota suspension) and 1 enema of placebo administered 7 days apart
Outcomes
Primary Outcome Measures
Treatment Success of Group A (2 Doses of RBX2660) vs Group B (2 Doses of Placebo) (ITT)
The primary endpoint is to evaluate treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema, of Group A (two enemas of RBX2660) vs. Group B (two enemas of placebo).
Secondary Outcome Measures
Treatment Success Between Group C (1 Enema of RBX2660 and 1 Enema of Placebo) vs Group B (Two Enemas of Placebo) (ITT)
Treatment Success was defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema
Treatment Success Evaluated Between Group A (Two Enemas of RBX2660) Versus Group C (1 Enema of RBX2660 and 1 Enema of Placebo) (ITT)
Treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema.
SF-36 Scores Obtained at the 1-week, 4-week, and 8-week Assessments Visits During the Double-blind Period as Compared to Baseline (ITT)
The validated SF-36 scale was used to identify changes to quality of life (QoL) following study treatment. Each component is analyzed on a norm-based scoring (0-100) with a higher score representing an improvement in QoL.
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group B (ITT)
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group C vs. Group B (ITT)
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group C (ITT)
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02299570
Brief Title
Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection
Acronym
PUNCHCD2
Official Title
A Phase 2B Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study Demonstrating the Efficacy and Safety of Rebiotix RBX2660 (Microbiota Suspension) for the Treatment of Recurrent Clostridium Difficile Infection
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
December 2014 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rebiotix Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. Patients who have had at least two recurrences of C. difficile infection (CDI) 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 CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.
Detailed Description
This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 compared to placebo at 8 weeks and (ii) safety via assessment of adverse events. Study visits are at 1-, 4- and 8-weeks after treatment with additional follow-up at 3, 6 12 and 24 months post treatment. Patients who have had at least two recurrences of C. difficile infection (CDI) 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 CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Enterocolitis Clostridium Difficile Recurrent
Keywords
Clostridium difficile, C diff, CDI, CDAD, Fecal transplant, Fecal Microbiota Transplant, Diarrhea, FMT, Microbiota restoration therapy, Microbiota suspension, Fecal bacteriotherapy, C diff diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Active Comparator
Arm Description
Two enemas of RBX2660 (microbiota suspension) administered 7 days apart
Arm Title
Group B
Arm Type
Placebo Comparator
Arm Description
Two enemas of placebo administered 7 days apart
Arm Title
Group C
Arm Type
Active Comparator
Arm Description
1 enema of RBX2660 (microbiota suspension) and 1 enema of placebo administered 7 days apart
Intervention Type
Biological
Intervention Name(s)
RBX2660 (microbiota suspension)
Intervention Description
A suspension of intestinal microbes
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
A suspension of saline and cryoprotectant
Primary Outcome Measure Information:
Title
Treatment Success of Group A (2 Doses of RBX2660) vs Group B (2 Doses of Placebo) (ITT)
Description
The primary endpoint is to evaluate treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema, of Group A (two enemas of RBX2660) vs. Group B (two enemas of placebo).
Time Frame
8 weeks after last assigned study treatment
Secondary Outcome Measure Information:
Title
Treatment Success Between Group C (1 Enema of RBX2660 and 1 Enema of Placebo) vs Group B (Two Enemas of Placebo) (ITT)
Description
Treatment Success was defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema
Time Frame
8-weeks
Title
Treatment Success Evaluated Between Group A (Two Enemas of RBX2660) Versus Group C (1 Enema of RBX2660 and 1 Enema of Placebo) (ITT)
Description
Treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema.
Time Frame
8-weeks
Title
SF-36 Scores Obtained at the 1-week, 4-week, and 8-week Assessments Visits During the Double-blind Period as Compared to Baseline (ITT)
Description
The validated SF-36 scale was used to identify changes to quality of life (QoL) following study treatment. Each component is analyzed on a norm-based scoring (0-100) with a higher score representing an improvement in QoL.
Time Frame
8-week
Title
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group B (ITT)
Description
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Time Frame
8-weeks
Title
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group C vs. Group B (ITT)
Description
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Time Frame
8-weeks
Title
Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group C (ITT)
Description
Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema.
Time Frame
8-weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years
Medical record documentation of recurrent CDI 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 C. difficile diarrhea while taking on a course of antibiotics prescribed for CDI treatment.
Requires antibiotic therapy for a condition other than recurrent CDI.
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.
Colostomy.
Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
Life expectancy of < 12 months.
Compromised immune system.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teena Chopra, MD MPH
Organizational Affiliation
Wayne State University
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Borland-Groover Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Grand Teton Research Group
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Loyola University Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Infectious Diseases of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Chevy Chase Clinical Research
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York Hospital Queens
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
Facility Name
New York-Presbyterian Hospital/Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Gastroenterology Group of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
Facility Name
Sanford Health
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
Louis Stokes Cleveland VA Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Regional Infectious Diseases and Infusion Center
City
Lima
State/Province
Ohio
ZIP/Postal Code
45801
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
St. Joseph's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
23323867
Citation
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.
Results Reference
background
PubMed Identifier
25232572
Citation
Moayyedi P, Marshall JK, Yuan Y, Hunt R. Canadian Association of Gastroenterology position statement: fecal microbiota transplant therapy. Can J Gastroenterol Hepatol. 2014 Feb;28(2):66-8. doi: 10.1155/2014/346590. No abstract available.
Results Reference
background
PubMed Identifier
22002980
Citation
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.
Results Reference
background
PubMed Identifier
32862830
Citation
Kwak S, Choi J, Hink T, Reske KA, Blount K, Jones C, Bost MH, Sun X, Burnham CD, Dubberke ER, Dantas G; CDC Prevention Epicenter Program. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome. 2020 Aug 31;8(1):125. doi: 10.1186/s40168-020-00907-9.
Results Reference
derived
PubMed Identifier
29617739
Citation
Dubberke ER, Lee CH, Orenstein R, Khanna S, Hecht G, Gerding DN. Results From a Randomized, Placebo-Controlled Clinical Trial of a RBX2660-A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection. Clin Infect Dis. 2018 Sep 28;67(8):1198-1204. doi: 10.1093/cid/ciy259.
Results Reference
derived
Links:
URL
http://www.rebiotix.com
Description
Sponsor website
Learn more about this trial
Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection
We'll reach out to this number within 24 hrs