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Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

Primary Purpose

Clostridium Difficile Infection (CDI)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
RBX2660
Placebo
Open label RBX2660 (only for confirmed CDI recurrence)
Sponsored by
Rebiotix Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile Infection (CDI) focused on measuring C Difficile Colitis, Clostridium Difficile, CDI, C.Difficile Diarrhea, Fecal Transplant, Fecal Microbiota Transplant (FMT), Microbiota Restoration Therapy, Diarrhea, FMT, Microbial Suspension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. ≥ 18 years old.
  2. 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.
  3. A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.
  4. 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]

Exclusion Criteria:

  1. Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.
  2. Previous fecal transplant
  3. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
  4. Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.
  5. Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy)
  6. An absolute neutrophil count of <1000 cells/µL during screening.
  7. Pregnant, breastfeeding, or intends to become pregnant during study participation.

Sites / Locations

  • Athens
  • Dothan
  • Phoenix
  • North Little Rock
  • Lancaster
  • Los Angeles
  • Oxnard
  • Sacramento
  • Aurora
  • Hamden
  • Gainesville
  • Jacksonville
  • Miami
  • Port Orange
  • Atlanta
  • Atlanta
  • Idaho Falls
  • Gurnee
  • Highland Park
  • Maywood
  • Lafayette
  • Topeka
  • Wichita
  • Lexington
  • New Orleans
  • Shreveport
  • Boston
  • Detroit
  • Plymouth
  • Rochester
  • St. Louis
  • Omaha
  • Omaha
  • Las Vegas
  • Teaneck
  • New York
  • North Massapequa
  • Rochester
  • Durham
  • Greenville
  • Wilmington
  • Fargo
  • Toledo
  • Portland
  • Flourtown
  • Philadelphia
  • Philadelphia
  • Uniontown
  • Wyomissing
  • Charleston
  • Rapid City
  • Hixson
  • Dallas
  • Houston
  • West Jordan
  • Springfield
  • Winchester
  • Seattle
  • Madison
  • Marshfield
  • Calgary
  • Edmonton
  • Vancouver
  • Victoria
  • Fredericton
  • Moncton

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

RBX2660

Arm Description

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 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant

Outcomes

Primary Outcome Measures

Efficacy of RBX2660 Compared to Placebo Through 8 Weeks
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

Sustained Clinical Response Through 6 Months After Blinded 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

Full Information

First Posted
August 2, 2017
Last Updated
August 10, 2023
Sponsor
Rebiotix Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03244644
Brief Title
Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)
Official Title
A Phase 3 Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of RBX2660 (Microbiota Suspension) for the Prevention of Clostridium Difficile Infection
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
July 31, 2017 (Actual)
Primary Completion Date
April 2, 2020 (Actual)
Study Completion Date
August 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rebiotix Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection (CDI)
Keywords
C Difficile Colitis, Clostridium Difficile, CDI, C.Difficile Diarrhea, Fecal Transplant, Fecal Microbiota Transplant (FMT), Microbiota Restoration Therapy, Diarrhea, FMT, Microbial Suspension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
320 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding
Arm Title
RBX2660
Arm Type
Experimental
Arm Description
RBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant
Intervention Type
Drug
Intervention Name(s)
RBX2660
Other Intervention Name(s)
microbiota suspension
Intervention Description
RBX2660 is a rectally administered microbiota suspension
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
saline solution
Intervention Description
Placebo is normal saline solution administered rectally
Intervention Type
Drug
Intervention Name(s)
Open label RBX2660 (only for confirmed CDI recurrence)
Other Intervention Name(s)
microbiota suspension
Intervention Description
RBX2660 administered as a second treatment after confirmed CDI recurrence following the initial dose of placebo or RBX2660
Primary Outcome Measure Information:
Title
Efficacy of RBX2660 Compared to Placebo Through 8 Weeks
Description
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.
Time Frame
8 weeks after completing the study treatment
Secondary Outcome Measure Information:
Title
Sustained Clinical Response Through 6 Months After Blinded Treatment
Description
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
Time Frame
6 months after completing the study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 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] Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teena Chopra, M.D., M.P.H.
Organizational Affiliation
Wayne State University
Official's Role
Study Chair
Facility Information:
Facility Name
Athens
City
Athens
State/Province
Alabama
ZIP/Postal Code
35611
Country
United States
Facility Name
Dothan
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36305
Country
United States
Facility Name
Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
North Little Rock
City
North Little Rock
State/Province
Arkansas
ZIP/Postal Code
72117
Country
United States
Facility Name
Lancaster
City
Lancaster
State/Province
California
ZIP/Postal Code
93534
Country
United States
Facility Name
Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Oxnard
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Aurora
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Hamden
City
Hamden
State/Province
Connecticut
ZIP/Postal Code
06518
Country
United States
Facility Name
Gainesville
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Port Orange
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Idaho Falls
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Gurnee
City
Gurnee
State/Province
Illinois
ZIP/Postal Code
60031
Country
United States
Facility Name
Highland Park
City
Highland Park
State/Province
Illinois
ZIP/Postal Code
60035
Country
United States
Facility Name
Maywood
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Lafayette
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47904
Country
United States
Facility Name
Topeka
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
Facility Name
Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Lexington
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71105
Country
United States
Facility Name
Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Detroit
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Plymouth
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55446
Country
United States
Facility Name
Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-4031
Country
United States
Facility Name
Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Las Vegas
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Teaneck
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
New York
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
North Massapequa
City
North Massapequa
State/Province
New York
ZIP/Postal Code
11758
Country
United States
Facility Name
Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
Facility Name
Durham
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Greenville
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Wilmington
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Fargo
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58102
Country
United States
Facility Name
Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Portland
City
Portland
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Flourtown
City
Flourtown
State/Province
Pennsylvania
ZIP/Postal Code
19031
Country
United States
Facility Name
Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
Facility Name
Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107-5244
Country
United States
Facility Name
Uniontown
City
Uniontown
State/Province
Pennsylvania
ZIP/Postal Code
15401
Country
United States
Facility Name
Wyomissing
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Charleston
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Rapid City
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Hixson
City
Hixson
State/Province
Tennessee
ZIP/Postal Code
37434
Country
United States
Facility Name
Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
West Jordan
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
Facility Name
Springfield
City
Springfield
State/Province
Virginia
ZIP/Postal Code
22150
Country
United States
Facility Name
Winchester
City
Winchester
State/Province
Virginia
ZIP/Postal Code
22601
Country
United States
Facility Name
Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Marshfield
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N2T9
Country
Canada
Facility Name
Edmonton
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
TG2X8
Country
Canada
Facility Name
Vancouver
City
Vancouver
State/Province
British Columba
ZIP/Postal Code
V5Z1M9
Country
Canada
Facility Name
Victoria
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
BC V8R 1J8
Country
Canada
Facility Name
Fredericton
City
Fredericton
State/Province
New Brunswick
ZIP/Postal Code
E3B 4R3
Country
Canada
Facility Name
Moncton
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C628
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
26031677
Citation
Bakken JS. Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations. Microb Ecol Health Dis. 2015 May 29;26:27657. doi: 10.3402/mehd.v26.27657. eCollection 2015. No abstract available.
Results Reference
background
PubMed Identifier
13592638
Citation
EISEMAN B, SILEN W, BASCOM GS, KAUVAR AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958 Nov;44(5):854-9. No abstract available.
Results Reference
background
PubMed Identifier
23530807
Citation
Miller MA, Louie T, Mullane K, Weiss K, Lentnek A, Golan Y, Kean Y, Sears P. Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect Dis. 2013 Mar 25;13:148. doi: 10.1186/1471-2334-13-148.
Results Reference
background
PubMed Identifier
36287379
Citation
Khanna S, Assi M, Lee C, Yoho D, Louie T, Knapple W, Aguilar H, Garcia-Diaz J, Wang GP, Berry SM, Marion J, Su X, Braun T, Bancke L, Feuerstadt P. Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs. 2022 Oct;82(15):1527-1538. doi: 10.1007/s40265-022-01797-x. Epub 2022 Oct 26. Erratum In: Drugs. 2022 Nov 7;:
Results Reference
derived
Links:
URL
https://www.cdc.gov/hai/eip/cdiff-tracking.html
Description
Centers for Disease Control page last reviewed March 15, 2021; accessed March 01, 2022.
URL
http://www.rebiotix.com
Description
Sponsor website
URL
https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-september-22-2022-meeting-announcement
Description
Rebyota sponsor briefing book

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Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

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