Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

NCT03244644 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2017-01
• Study Type: interventional
• Target: 320
• Locations: 2 countries
• Sites: 66

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  8 weeks after completing the study treatment

Secondary Outcomes (1)

• Sustained Clinical Response Through 6 Months After Blinded Treatment

  6 months after completing the study treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding

Drug: Placebo; Drug: Open label RBX2660 (only for confirmed CDI recurrence)

RBX2660

EXPERIMENTAL

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

Drug: RBX2660; Drug: Open label RBX2660 (only for confirmed CDI recurrence)

Interventions

RBX2660 DRUG

RBX2660 is a rectally administered microbiota suspension

Also known as: microbiota suspension

RBX2660

Placebo DRUG

Placebo is normal saline solution administered rectally

Also known as: saline solution

Placebo

Open label RBX2660 (only for confirmed CDI recurrence) DRUG

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

Also known as: microbiota suspension

Placebo; RBX2660

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.
• \[Note: Subject's CDI diarrhea must be controlled (\<3 unformed/loose stools/day) while taking this course of antibiotics\]

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rebiotix Inc.: lead

Study Sites (66)

Athens

Athens, Alabama, 35611, United States

Location

Dothan

Dothan, Alabama, 36305, United States

Location

Phoenix

Phoenix, Arizona, 85054, United States

Location

North Little Rock

North Little Rock, Arkansas, 72117, United States

Location

Lancaster

Lancaster, California, 93534, United States

Location

Los Angeles

Los Angeles, California, 90095, United States

Location

Oxnard

Oxnard, California, 93030, United States

Location

Sacramento

Sacramento, California, 95817, United States

Location

Aurora

Aurora, Colorado, 80045, United States

Location

Hamden

Hamden, Connecticut, 06518, United States

Location

Gainesville

Gainesville, Florida, 32610, United States

Location

Jacksonville

Jacksonville, Florida, 32224, United States

Location

Miami

Miami, Florida, 33176, United States

Location

Port Orange

Port Orange, Florida, 32127, United States

Location

Atlanta

Atlanta, Georgia, 30322, United States

Location

Atlanta

Atlanta, Georgia, 30342, United States

Location

Idaho Falls

Idaho Falls, Idaho, 83404, United States

Location

Gurnee

Gurnee, Illinois, 60031, United States

Location

Highland Park

Highland Park, Illinois, 60035, United States

Location

Maywood

Maywood, Illinois, 60153, United States

Location

Lafayette

Lafayette, Indiana, 47904, United States

Location

Topeka

Topeka, Kansas, 66606, United States

Location

Wichita

Wichita, Kansas, 67214, United States

Location

Lexington

Lexington, Kentucky, 40536, United States

Location

New Orleans

New Orleans, Louisiana, 70121, United States

Location

Shreveport

Shreveport, Louisiana, 71105, United States

Location

Boston

Boston, Massachusetts, 02114, United States

Location

Detroit

Detroit, Michigan, 48202, United States

Location

Plymouth

Plymouth, Minnesota, 55446, United States

Location

Rochester

Rochester, Minnesota, 55902, United States

Location

St. Louis

St Louis, Missouri, 63110, United States

Location

Omaha

Omaha, Nebraska, 68198-4031, United States

Location

Omaha

Omaha, Nebraska, 68198, United States

Location

Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Teaneck

Teaneck, New Jersey, 07666, United States

Location

New York

New York, New York, 10016, United States

Location

North Massapequa

North Massapequa, New York, 11758, United States

Location

Rochester

Rochester, New York, 14618, United States

Location

Durham

Durham, North Carolina, 27710, United States

Location

Greenville

Greenville, North Carolina, 27834, United States

Location

Wilmington

Wilmington, North Carolina, 28401, United States

Location

Fargo

Fargo, North Dakota, 58102, United States

Location

Toledo

Toledo, Ohio, 43608, United States

Location

Portland

Portland, Oregon, 97701, United States

Location

Flourtown

Flourtown, Pennsylvania, 19031, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19102, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19107-5244, United States

Location

Uniontown

Uniontown, Pennsylvania, 15401, United States

Location

Wyomissing

Wyomissing, Pennsylvania, 19610, United States

Location

Charleston

Charleston, South Carolina, 29425, United States

Location

Rapid City

Rapid City, South Dakota, 57701, United States

Location

Hixson

Hixson, Tennessee, 37434, United States

Location

Dallas

Dallas, Texas, 75246, United States

Location

Houston

Houston, Texas, 77030, United States

Location

West Jordan

West Jordan, Utah, 84088, United States

Location

Springfield

Springfield, Virginia, 22150, United States

Location

Winchester

Winchester, Virginia, 22601, United States

Location

Seattle

Seattle, Washington, 98104, United States

Location

Madison

Madison, Wisconsin, 53792, United States

Location

Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Calgary

Calgary, Alberta, T2N2T9, Canada

Location

Edmonton

Edmonton, Alberta, TG2X8, Canada

Location

Vancouver

Vancouver, British Columba, V5Z1M9, Canada

Location

Victoria

Victoria, British Columbia, BC V8R 1J8, Canada

Location

Fredericton

Fredericton, New Brunswick, E3B 4R3, Canada

Location

Moncton

Moncton, New Brunswick, E1C628, Canada

Location

Related Publications (11)

• 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.

  PMID: 26031677 BACKGROUND

• 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.

  PMID: 13592638 BACKGROUND

• 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.

  PMID: 23530807 BACKGROUND

• Lee C, Feuerstadt P, Louie T, Bancke L, Guthmueller B, Harvey A, Hoeyer F, Orenstein R, Dubberke ER, Khanna S. Integrated analysis of the safety of fecal microbiota, live-jslm in adults with recurrent Clostridioides difficile infection from five prospective clinical trials: an update. Therap Adv Gastroenterol. 2025 Nov 12;18:17562848251395566. doi: 10.1177/17562848251395566. eCollection 2025.

  PMID: 41245385 DERIVED

• 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 Dec;96:103006. doi: 10.1016/j.anaerobe.2025.103006. Epub 2025 Oct 18.

  PMID: 41115624 DERIVED

• 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.

  PMID: 40672762 DERIVED

• 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.

  PMID: 40552763 DERIVED

• 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.

  PMID: 39172632 DERIVED

• 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.

  PMID: 38236515 DERIVED

• 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.

  PMID: 37564743 DERIVED

• 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.

  PMID: 36287379 DERIVED

Related Links

• Centers for Disease Control page last reviewed March 15, 2021; accessed March 01, 2022.
• Sponsor website
• Rebyota sponsor briefing book

MeSH Terms

Conditions

Clostridium Infections; Enterocolitis, Pseudomembranous; Diarrhea

Interventions

Saline Solution; Single Person

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Results Point of Contact

• Title: Clinical Development
• Organization: Rebiotix inc, a Ferring Company

US8-StudyInfo@ferring.com

651-705-8778

Study Officials

• Teena Chopra, M.D., M.P.H.

  Wayne State University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 9, 2017
• Study Start: July 31, 2017
• Primary Completion: April 2, 2020
• Study Completion: August 3, 2020
• Last Updated: July 10, 2024
• Results First Posted: August 14, 2023

Record last verified: 2024-07

Locations

US (60); CA (6)