Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCH CD3-OLS)

NCT ID: NCT03931941

Last Updated: 2024-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 793 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-30
• Study Completion Date: 2023-07-21

Brief Summary

This is a prospective, multicenter, open-label Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence of CDI 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 may be eligible for the study. Subjects may receive a second RBX2660 enema if they are deemed treatment failures following the initial enema per the protocol-specified treatment failure definition.

Detailed Description

This is a prospective, multicenter, open-label Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) safety via assessment of treatment-emergent adverse events and (ii) efficacy of RBX2660 preventing recurrent episodes of CDI measured at 8 weeks after treatment. Follow-up office visits occur at 1 week and 8 weeks after completing the initial study treatment. Telephone assessments occur at 4 weeks, and 4 and 6 months after the study. Patients who have had at least one recurrence of CDI 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 may be eligible for the study. Subjects may receive a second RBX2660 enema if they are deemed treatment failures following the initial enema per the protocol-specified treatment failure definition.

Conditions

Clostridium Difficile Infection; Infection; Communicable Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active

RBX2660 is an enema of a microbiota suspension

Group Type: EXPERIMENTAL

RBX2660

Intervention Type: DRUG

RBX2660 is a microbiota suspension administered as an enema

Interventions

RBX2660

RBX2660 is a microbiota suspension administered as an enema

Intervention Type: DRUG

Other Intervention Names

Microbiota suspension

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years old.

2. Medical record documentation of either: a) a current diagnosis or history of recurrent CDI as determined by the treating physician, b) or has had at least two episodes of severe CDI resulting in hospitalization.

3. 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 antibiotics during screening.]

Exclusion Criteria

1. Has continued CDI diarrhea despite being on a course of antibiotics prescribed for CDI treatment.

2. Requires systemic antibiotic therapy for a condition other than CDI.

3. Fecal microbiota transplant (FMT) within the past 6 months.

4. FMT with an associated serious adverse event related to the FMT product or procedure.

5. Bezlotoxumab (CDI monoclonal antibodies) if received within the last year.

6. CD4 count <200/mm^3 during Screening.

7. An absolute neutrophil count of <1000 cells/µL during Screening.

8. Pregnant, breastfeeding, or intends to become pregnant during study participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rebiotix Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Role: STUDY_CHAIR

Wayne State University

Locations

Phoenix

Phoenix, Arizona, United States

North Little Rock

North Little Rock, Arkansas, United States

Oxnard

Oxnard, California, United States

Aurora

Aurora, Colorado, United States

Hamden

Hamden, Connecticut, United States

Gainesville

Gainesville, Florida, United States

Jacksonville

Jacksonville, Florida, United States

Naples

Naples, Florida, United States

Orlando

Orlando, Florida, United States

Port Orange

Port Orange, Florida, United States

Atlanta

Atlanta, Georgia, United States

Decatur

Decatur, Georgia, United States

Idaho Falls

Idaho Falls, Idaho, United States

Burr Ridge

Burr Ridge, Illinois, United States

Gurnee

Gurnee, Illinois, United States

Fort Wayne

Fort Wayne, Indiana, United States

Wichita

Wichita, Kansas, United States

New Orleans

New Orleans, Louisiana, United States

Shreveport

Shreveport, Louisiana, United States

Baltimore

Baltimore, Maryland, United States

Detroit

Detroit, Michigan, United States

Plymouth

Plymouth, Minnesota, United States

Rochester

Rochester, Minnesota, United States

St. Louis

St Louis, Missouri, United States

New York

New York, New York, United States

Rochester

Rochester, New York, United States

Durham

Durham, North Carolina, United States

Fargo

Fargo, North Dakota, United States

Cleveland

Cleveland, Ohio, United States

Oklahoma City

Oklahoma City, Oklahoma, United States

Philadelphia

Philadelphia, Pennsylvania, United States

Pittsburgh

Pittsburgh, Pennsylvania, United States

Wyomissing

Wyomissing, Pennsylvania, United States

Charleston

Charleston, South Carolina, United States

Hixon

Hixon, Tennessee, United States

Nashville

Nashville, Tennessee, United States

Dallas

Dallas, Texas, United States

Houston

Houston, Texas, United States

West Jordan

West Jordan, Utah, United States

Annandale

Annandale, Virginia, United States

Springfield

Springfield, Virginia, United States

Seattle

Seattle, Washington, United States

Spokane

Spokane, Washington, United States

Madison

Madison, Wisconsin, United States

Marshfield

Marshfield, Wisconsin, United States

Milwaukee

Milwaukee, Wisconsin, United States

Calgary

Calgary, Alberta, Canada

Edmonton

Edmonton, Alberta, Canada

Vancouver

Vancouver, British Columbia, Canada

Victoria

Victoria, British Columbia, Canada

Moncton

Moncton, New Brunswick, Canada

Countries

United States; Canada

References

Aroniadis OC, Guthmueller B, Dehlin K, Srivastava S, Feuerstadt P, Lembo A, Weber HC. Safety and Efficacy of Fecal Microbiota, Live-jslm to Prevent Recurrent Clostridioides difficile Infection in Participants With Irritable Bowel Syndrome. Infect Dis Ther. 2025 Sep;14(9):2157-2169. doi: 10.1007/s40121-025-01208-0. Epub 2025 Aug 10.

Reference Type: DERIVED

PMID: 40784972 (View on PubMed)

Alonso CD, Tillotson GS, Bidell MR, Guthmueller B, Hoeyer F, Fischer M, Dubberke ER. Safety and Efficacy of Fecal Microbiota, Live-jslm, in Preventing Recurrent Clostridioides difficile Infection in Participants Who Were Mildly to Moderately Immunocompromised in the Phase 3 PUNCH CD3-OLS Study. Open Forum Infect Dis. 2025 Mar 4;12(4):ofaf117. doi: 10.1093/ofid/ofaf117. eCollection 2025 Apr.

Reference Type: DERIVED

PMID: 40177588 (View on PubMed)

Feuerstadt P, Chopra T, Knapple W, Van Hise NW, Dubberke ER, Baggott B, Guthmueller B, Bancke L, Gamborg M, Steiner TS, Van Handel D, Khanna S. PUNCH CD3-OLS: A Phase 3 Prospective Observational Cohort Study to Evaluate the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA) in Adults With Recurrent Clostridioides difficile Infection. Clin Infect Dis. 2025 Feb 5;80(1):43-51. doi: 10.1093/cid/ciae437.

Reference Type: DERIVED

PMID: 39180326 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-01

Identifier Type: -

Identifier Source: org_study_id