Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

NCT ID: NCT03244644

Last Updated: 2024-07-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-31

Study Completion Date

2020-08-03

Brief Summary

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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

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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.

Conditions

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Clostridium Difficile Infection (CDI)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo is normal saline solution administered rectally

Open label RBX2660 (only for confirmed CDI recurrence)

Intervention Type DRUG

RBX2660 administered as a second treatment after confirmed CDI recurrence following the initial dose of placebo or RBX2660

RBX2660

RBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant

Group Type EXPERIMENTAL

RBX2660

Intervention Type DRUG

RBX2660 is a rectally administered microbiota suspension

Open label RBX2660 (only for confirmed CDI recurrence)

Intervention Type DRUG

RBX2660 administered as a second treatment after confirmed CDI recurrence following the initial dose of placebo or RBX2660

Interventions

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RBX2660

RBX2660 is a rectally administered microbiota suspension

Intervention Type DRUG

Placebo

Placebo is normal saline solution administered rectally

Intervention Type DRUG

Open label RBX2660 (only for confirmed CDI recurrence)

RBX2660 administered as a second treatment after confirmed CDI recurrence following the initial dose of placebo or RBX2660

Intervention Type DRUG

Other Intervention Names

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microbiota suspension saline solution microbiota suspension

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rebiotix Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Teena Chopra, M.D., M.P.H.

Role: STUDY_CHAIR

Wayne State University

Locations

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Athens

Athens, Alabama, United States

Site Status

Dothan

Dothan, Alabama, United States

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Phoenix

Phoenix, Arizona, United States

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North Little Rock

North Little Rock, Arkansas, United States

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Lancaster

Lancaster, California, United States

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Los Angeles

Los Angeles, California, United States

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Oxnard

Oxnard, California, United States

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Sacramento

Sacramento, California, United States

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Aurora

Aurora, Colorado, United States

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Hamden

Hamden, Connecticut, United States

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Gainesville

Gainesville, Florida, United States

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Jacksonville

Jacksonville, Florida, United States

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Miami

Miami, Florida, United States

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Port Orange

Port Orange, Florida, United States

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Atlanta

Atlanta, Georgia, United States

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Atlanta

Atlanta, Georgia, United States

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Idaho Falls

Idaho Falls, Idaho, United States

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Gurnee

Gurnee, Illinois, United States

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Highland Park

Highland Park, Illinois, United States

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Maywood

Maywood, Illinois, United States

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Lafayette

Lafayette, Indiana, United States

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Topeka

Topeka, Kansas, United States

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Wichita

Wichita, Kansas, United States

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Lexington

Lexington, Kentucky, United States

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New Orleans

New Orleans, Louisiana, United States

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Shreveport

Shreveport, Louisiana, United States

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Boston

Boston, Massachusetts, United States

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Detroit

Detroit, Michigan, United States

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Plymouth

Plymouth, Minnesota, United States

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Rochester

Rochester, Minnesota, United States

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St. Louis

St Louis, Missouri, United States

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Omaha

Omaha, Nebraska, United States

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Omaha

Omaha, Nebraska, United States

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Las Vegas

Las Vegas, Nevada, United States

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Teaneck

Teaneck, New Jersey, United States

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New York

New York, New York, United States

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North Massapequa

North Massapequa, New York, United States

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Rochester

Rochester, New York, United States

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Durham

Durham, North Carolina, United States

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Greenville

Greenville, North Carolina, United States

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Wilmington

Wilmington, North Carolina, United States

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Fargo

Fargo, North Dakota, United States

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Toledo

Toledo, Ohio, United States

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Portland

Portland, Oregon, United States

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Flourtown

Flourtown, Pennsylvania, United States

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Philadelphia

Philadelphia, Pennsylvania, United States

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Philadelphia

Philadelphia, Pennsylvania, United States

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Uniontown

Uniontown, Pennsylvania, United States

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Wyomissing

Wyomissing, Pennsylvania, United States

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Charleston

Charleston, South Carolina, United States

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Rapid City

Rapid City, South Dakota, United States

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Hixson

Hixson, Tennessee, United States

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Dallas

Dallas, Texas, United States

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Houston

Houston, Texas, United States

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West Jordan

West Jordan, Utah, United States

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Springfield

Springfield, Virginia, United States

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Winchester

Winchester, Virginia, United States

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Seattle

Seattle, Washington, United States

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Madison

Madison, Wisconsin, United States

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Marshfield

Marshfield, Wisconsin, United States

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Calgary

Calgary, Alberta, Canada

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Edmonton

Edmonton, Alberta, Canada

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Vancouver

Vancouver, British Columba, Canada

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Victoria

Victoria, British Columbia, Canada

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Fredericton

Fredericton, New Brunswick, Canada

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Moncton

Moncton, New Brunswick, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 26031677 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 13592638 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23530807 (View on PubMed)

Mishra R, Harvey A, Guo A, Tillotson G, Feuerstadt P, Khanna S, Shannon WD, Blount KF. Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements. Anaerobe. 2025 Oct 18:103006. doi: 10.1016/j.anaerobe.2025.103006. Online ahead of print.

Reference Type DERIVED
PMID: 41115624 (View on PubMed)

Adamowicz E, Kraft CS, Ward T, Mehta N, Shannon WD, Mishra R, Blount KF. Decreased Antimicrobial Resistance Gene Richness Following Fecal Microbiota, Live-jslm (REBYOTA(R)) Administration: Post Hoc Analysis of PUNCH CD3. Open Forum Infect Dis. 2025 Jul 2;12(7):ofaf382. doi: 10.1093/ofid/ofaf382. eCollection 2025 Jul.

Reference Type DERIVED
PMID: 40672762 (View on PubMed)

Claypool J, Lindved G, Myers PN, Ward T, Nielsen HB, Blount KF. Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection. Gut Microbes. 2025 Dec;17(1):2520412. doi: 10.1080/19490976.2025.2520412. Epub 2025 Jun 24.

Reference Type DERIVED
PMID: 40552763 (View on PubMed)

Blount KF, Papazyan R, Ferdyan N, Srinivasan K, Gonzalez C, Shannon WD, Fuchs BC. Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA) for Preventing Recurrent Clostridioides difficile Infection. J Infect Dis. 2025 Jul 11;231(6):e1022-e1033. doi: 10.1093/infdis/jiae418.

Reference Type DERIVED
PMID: 39172632 (View on PubMed)

Feuerstadt P, Allegretti JR, Dubberke ER, Guo A, Harvey A, Yang M, Garcia-Horton V, Fillbrunn M, Tillotson G, Bancke LL, LaPlante K, Garey KW, Khanna S. Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection. Infect Dis Ther. 2024 Jan;13(1):221-236. doi: 10.1007/s40121-023-00907-w. Epub 2024 Jan 18.

Reference Type DERIVED
PMID: 38236515 (View on PubMed)

Garey KW, Dubberke ER, Guo A, Harvey A, Yang M, Garcia-Horton V, Fillbrunn M, Wang H, Tillotson GS, Bancke LL, Feuerstadt P. Effect of Fecal Microbiota, Live-Jslm (REBYOTA [RBL]) on Health-Related Quality of Life in Patients With Recurrent Clostridioides difficile Infection: Results From the PUNCH CD3 Clinical Trial. Open Forum Infect Dis. 2023 Jul 20;10(8):ofad383. doi: 10.1093/ofid/ofad383. eCollection 2023 Aug.

Reference Type DERIVED
PMID: 37564743 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36287379 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Other Identifiers

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2017-01

Identifier Type: -

Identifier Source: org_study_id

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