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Clostridium Difficile InfectionPhase 3CD3-OLSNCT03931941

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

A Phase 3 study testing RBX2660 in people with Clostridium Difficile Infection and Infection, run by Rebiotix Inc. at 51 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RBX2660
Could I receive a placebo?
No, everyone receives an active treatment
How many people
793 participants
Where
51 sitesin 2 countries
Study dates
30 Jul 2019to 21 Jul 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years old.
  • 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.
  • 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.]

Who cannot join

  • Has continued CDI diarrhea despite being on a course of antibiotics prescribed for CDI treatment.
  • Requires systemic antibiotic therapy for a condition other than CDI.
  • Fecal microbiota transplant (FMT) within the past 6 months.
  • FMT with an associated serious adverse event related to the FMT product or procedure.
  • Bezlotoxumab (CDI monoclonal antibodies) if received within the last year.
  • CD4 count <200/mm^3 during Screening.
  • An absolute neutrophil count of <1000 cells/µL during Screening.
  • Pregnant, breastfeeding, or intends to become pregnant during study participation.

Trial locations and contacts

51 sites in 2 countries.

51 sites in 2 countries

United States46 sites

  • Annandale

    Annandale, Virginia, 22003

  • Atlanta

    Atlanta, Georgia, 30309

  • Aurora

    Aurora, Colorado, 80045

  • Baltimore

    Baltimore, Maryland, 21215

  • Burr Ridge

    Burr Ridge, Illinois, 60527

  • Charleston

    Charleston, South Carolina, 29425

  • Cleveland

    Cleveland, Ohio, 44195

  • Dallas

    Dallas, Texas, 75246

  • Decatur

    Decatur, Georgia, 30033

  • Detroit

    Detroit, Michigan, 48202

  • Durham

    Durham, North Carolina, 27710

  • Fargo

    Fargo, North Dakota, 58122

  • Fort Wayne

    Fort Wayne, Indiana, 46845

  • Gainesville

    Gainesville, Florida, 32610

  • Gurnee

    Gurnee, Illinois, 60035

  • Hamden

    Hamden, Connecticut, 06518

  • Hixon

    Hixon, Tennessee, 37434

  • Houston

    Houston, Texas, 77030

  • Idaho Falls

    Idaho Falls, Idaho, 83404

  • Jacksonville

    Jacksonville, Florida, 32224

  • Madison

    Madison, Wisconsin, 53704

  • Marshfield

    Marshfield, Wisconsin, 54449

  • Milwaukee

    Milwaukee, Wisconsin, 53215

  • Naples

    Naples, Florida, 34102

  • Nashville

    Nashville, Tennessee, 37212

  • New Orleans

    New Orleans, Louisiana, 70121

  • New York

    New York, New York, 10016

  • North Little Rock

    North Little Rock, Arkansas, 72117

  • Oklahoma City

    Oklahoma City, Oklahoma, 73102

  • Orlando

    Orlando, Florida, 32806

  • Oxnard

    Oxnard, California, 93030

  • Philadelphia

    Philadelphia, Pennsylvania, 19107

  • Phoenix

    Phoenix, Arizona, 85054

  • Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Plymouth

    Plymouth, Minnesota, 55446

  • Port Orange

    Port Orange, Florida, 32127

  • Rochester

    Rochester, Minnesota, 55905

  • Rochester

    Rochester, New York, 14618

  • Seattle

    Seattle, Washington, 98104

  • Shreveport

    Shreveport, Louisiana, 71105

  • Spokane

    Spokane, Washington, 99202

  • Springfield

    Springfield, Virginia, 22150

  • St. Louis

    St Louis, Missouri, 63110

  • West Jordan

    West Jordan, Utah, 84088

  • Wichita

    Wichita, Kansas, 67214

  • Wyomissing

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Canada5 sites

  • Calgary

    Calgary, Alberta, T2N 2T9

  • Edmonton

    Edmonton, Alberta, T6G 2X8

  • Moncton

    Moncton, New Brunswick, E1C 6Z8

  • Vancouver

    Vancouver, British Columbia, V5Z 1M9

  • Victoria

    Victoria, British Columbia, V8R 1J8

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
RBX2660
Keywords
C. Difficile Diarrhea, Clostridium Difficile, CDI, FMT, Fecal Microbiota Transplant, Microbiota Restoration Therapy, Diarrhea, Microbial Suspension, Fecal Transplant, C Difficile Colitis, Clostridium Difficile Associated Diarrhea, C diff diarrhea, C Difficile, C diff
Medical subject headings
Clostridium Infections, Infections, Communicable Diseases, Diarrhea, Enterocolitis, Pseudomembranous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RBX2660Drug

    Also called Microbiota suspension

    RBX2660 is a microbiota suspension administered as an enema

Study groups in NCT03931941
Study groupRoleWhat they receive
ActiveExperimentalRBX2660 is an enema of a microbiota suspension
Receives: Drug: RBX2660

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Up to 6 months after last study treatment.

Secondary outcomes (2)

  1. 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.

    Measured: 8 weeks after completing the study treatment

  2. 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.

    Measured: 6 months after completing the study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2019
  2. Study start30 Jul 2019
  3. Primary completion21 Jul 2023
  4. Study completion21 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
793 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03931941
Sponsor's protocol ID
2019-01
Acronym
CD3-OLS
Status last verified
Apr 2023
First submitted
26 Apr 2019
Last updated
7 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Steiner T, Louie T, Kao D, Smyth D, Guthmueller B, Jason T, Elliott SN, Srivastava S, Lee C. Evaluation of fecal microbiota, live (RBL) for the prevention of recurrent Clostridioides difficile infection: Canadian subgroup analysis of an open-label phase 3 study. J Can Assoc Gastroenterol. 2026 Jun 20;9(5):336-342. doi: 10.1093/jcag/gwag021. eCollection 2026 Oct.

    PubMed 42840322

  • Chopra T, Van Handel D, Baggott B, Orenstein R, Reveles K, Guthmueller B, Srivastava S, Khanna S. Efficacy Outcomes of Fecal Microbiota, Live-jslm in Preventing Recurrent Clostridioides difficile Infection from Seven Clinical Studies. Infect Dis Ther. 2026 Aug;15(8):2071-2086. doi: 10.1007/s40121-026-01374-9. Epub 2026 Jun 12.

    PubMed 42286373

  • Skinner AM, Lodise TP, Reilly J, Guthmueller B, Srivastava S, Axelrad JE. Safety and Efficacy of Fecal Microbiota, Live-jslm for Prevention of Recurrent Clostridioides difficile Infection Among Hospitalized Participants in PUNCH CD3-OLS. Infect Dis Ther. 2026 Mar;15(3):889-901. doi: 10.1007/s40121-026-01304-9. Epub 2026 Feb 7.

    PubMed 41653256

  • 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. Ther Adv Gastroenterol. 2025 Nov 12;18:17562848251395566. doi: 10.1177/17562848251395566. eCollection 2025.

    PubMed 41245385

  • 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.

    PubMed 40784972

  • 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.

    PubMed 40177588

  • 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.

    PubMed 39180326

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RBX2660 in people with Clostridium Difficile Infection and Infection, run by Rebiotix Inc. at 51 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of RBX2660 in Subjects With Recurrent CDI. (time frame: Up to 6 months after last study treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03931941, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.

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