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

A Phase 3 Open-Label Clinical Study to Evaluate the Safety and Tolerability of Rebiotix RBX2660 (Microbiota Suspension) in Subjects With Recurrent Clostridium Difficile Infection

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.

Study Overview

• Status: Completed
• Conditions: Communicable Diseases; Infection; Clostridium Difficile Infection
• Intervention / Treatment: Drug: RBX2660

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.

• Study Type: Interventional
• Enrollment (Actual): 817
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Calgary
    • Edmonton, Alberta, Canada, T6G 2X8
      • Edmonton
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver
    • Victoria, British Columbia, Canada, V8R 1J8
      • Victoria
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Phoenix
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • North Little Rock
  • California
    • Oxnard, California, United States, 93030
      • Oxnard
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Aurora
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Hamden
  • Florida
    • Gainesville, Florida, United States, 32610
      • Gainesville
    • Jacksonville, Florida, United States, 32224
      • Jacksonville
    • Naples, Florida, United States, 34102
      • Naples
    • Orlando, Florida, United States, 32806
      • Orlando
    • Port Orange, Florida, United States, 32127
      • Port Orange
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta
    • Decatur, Georgia, United States, 30033
      • Decatur
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Idaho Falls
  • Illinois
    • Burr Ridge, Illinois, United States, 60527
      • Burr Ridge
    • Gurnee, Illinois, United States, 60035
      • Gurnee
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • New Orleans
    • Shreveport, Louisiana, United States, 71105
      • Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Baltimore
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Detroit
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Plymouth
    • Rochester, Minnesota, United States, 55905
      • Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis
  • New York
    • New York, New York, United States, 10016
      • New York
    • Rochester, New York, United States, 14618
      • Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Durham
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Fargo
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Oklahoma City
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pittsburgh
    • Wyomissing, Pennsylvania, United States, 19610
      • Wyomissing
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Charleston
  • Tennessee
    • Hixon, Tennessee, United States, 37434
      • Hixon
    • Nashville, Tennessee, United States, 37212
      • Nashville
  • Texas
    • Dallas, Texas, United States, 75246
      • Dallas
    • Houston, Texas, United States, 77030
      • Houston
  • Utah
    • West Jordan, Utah, United States, 84088
      • West Jordan
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Annandale
    • Springfield, Virginia, United States, 22150
      • Springfield
  • Washington
    • Seattle, Washington, United States, 98104
      • Seattle
    • Spokane, Washington, United States, 99202
      • Spokane
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Madison
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield
    • Milwaukee, Wisconsin, United States, 53215
      • Milwaukee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; RBX2660 is an enema of a microbiota suspension	Drug: RBX2660; RBX2660 is a microbiota suspension administered as an enema; Other Names: Microbiota suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of RBX2660 in subjects with recurrent CDI.	Number of subjects with investigational product- and/or enema-related treatment-emergent adverse events (TEAEs).	Up to 6 months after last study treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of RBX2660 measured at 8 weeks after treatment.	The absence of C. difficile diarrhea without the need for retreatment through 8 weeks after administration of the study treatment.	8 weeks after completing the study treatment
Sustained clinical response through 6 months after treatment.	Treatment success of the presenting CDI recurrence and no new CDI episodes for greater than 8 weeks through 6 months after completing a study treatment assessed by subject phone interview up to 6 months after the last study treatment.	6 months after completing the study treatment

Collaborators and Investigators

• Sponsor: Rebiotix Inc.
• Investigators: Study Chair: Teena Chopra, M.D., M.P.H., Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Actual): July 21, 2023
• Study Completion (Actual): July 21, 2023

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Diarrhea; FMT; Clostridium Difficile; CDI; C diff; Microbiota Restoration Therapy; Fecal Microbiota Transplant; C Difficile; C Difficile Colitis; Fecal Transplant; Microbial Suspension; C diff diarrhea; C. Difficile Diarrhea; Clostridium Difficile Associated Diarrhea
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections
• Other Study ID Numbers: 2019-01 (Other Identifier: NANT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No