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Clostridium Difficile Infection (CDI)Phase 3NCT03244644

Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

A Phase 3 study testing RBX2660 and Open label RBX2660 (only for confirmed CDI recurrence) in people with Clostridium Difficile Infection (CDI), run by Rebiotix Inc. at 66 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, 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Clostridium Difficile Infection (CDI)
What is being tested?
RBX2660 and Open label RBX2660 (only for confirmed CDI recurrence)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
320 participants
Where
66 sitesin 2 countries
Study dates
31 Jul 2017to 3 Aug 2020
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 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]

Who cannot join

  • 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.

Trial locations and contacts

66 sites in 2 countries.

66 sites in 2 countries

United States60 sites

  • Athens

    Athens, Alabama, 35611

  • Atlanta

    Atlanta, Georgia, 30322

  • Atlanta

    Atlanta, Georgia, 30342

  • Aurora

    Aurora, Colorado, 80045

  • Boston

    Boston, Massachusetts, 02114

  • Charleston

    Charleston, South Carolina, 29425

  • Dallas

    Dallas, Texas, 75246

  • Detroit

    Detroit, Michigan, 48202

  • Dothan

    Dothan, Alabama, 36305

  • Durham

    Durham, North Carolina, 27710

  • Fargo

    Fargo, North Dakota, 58102

  • Flourtown

    Flourtown, Pennsylvania, 19031

  • Gainesville

    Gainesville, Florida, 32610

  • Greenville

    Greenville, North Carolina, 27834

  • Gurnee

    Gurnee, Illinois, 60031

  • Hamden

    Hamden, Connecticut, 06518

  • Highland Park

    Highland Park, Illinois, 60035

  • Hixson

    Hixson, Tennessee, 37434

  • Houston

    Houston, Texas, 77030

  • Idaho Falls

    Idaho Falls, Idaho, 83404

  • Jacksonville

    Jacksonville, Florida, 32224

  • Lafayette

    Lafayette, Indiana, 47904

  • Lancaster

    Lancaster, California, 93534

  • Las Vegas

    Las Vegas, Nevada, 89106

  • Lexington

    Lexington, Kentucky, 40536

  • Los Angeles

    Los Angeles, California, 90095

  • Madison

    Madison, Wisconsin, 53792

  • Marshfield

    Marshfield, Wisconsin, 54449

  • Maywood

    Maywood, Illinois, 60153

  • Miami

    Miami, Florida, 33176

  • New Orleans

    New Orleans, Louisiana, 70121

  • New York

    New York, New York, 10016

  • North Little Rock

    North Little Rock, Arkansas, 72117

  • North Massapequa

    North Massapequa, New York, 11758

  • Omaha

    Omaha, Nebraska, 68198-4031

  • Omaha

    Omaha, Nebraska, 68198

  • Oxnard

    Oxnard, California, 93030

  • Philadelphia

    Philadelphia, Pennsylvania, 19102

  • Philadelphia

    Philadelphia, Pennsylvania, 19107-5244

  • Phoenix

    Phoenix, Arizona, 85054

  • Plymouth

    Plymouth, Minnesota, 55446

  • Port Orange

    Port Orange, Florida, 32127

  • Portland

    Portland, Oregon, 97701

  • Rapid City

    Rapid City, South Dakota, 57701

  • Rochester

    Rochester, Minnesota, 55902

  • Rochester

    Rochester, New York, 14618

  • Sacramento

    Sacramento, California, 95817

  • Seattle

    Seattle, Washington, 98104

  • Shreveport

    Shreveport, Louisiana, 71105

  • Springfield

    Springfield, Virginia, 22150

  • St. Louis

    St Louis, Missouri, 63110

  • Teaneck

    Teaneck, New Jersey, 07666

  • Toledo

    Toledo, Ohio, 43608

  • Topeka

    Topeka, Kansas, 66606

  • Uniontown

    Uniontown, Pennsylvania, 15401

  • West Jordan

    West Jordan, Utah, 84088

  • Wichita

    Wichita, Kansas, 67214

  • Wilmington

    Wilmington, North Carolina, 28401

  • Winchester

    Winchester, Virginia, 22601

  • Wyomissing

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Canada6 sites

  • Calgary

    Calgary, Alberta, T2N2T9

  • Edmonton

    Edmonton, Alberta, TG2X8

  • Fredericton

    Fredericton, New Brunswick, E3B 4R3

  • Moncton

    Moncton, New Brunswick, E1C628

  • Vancouver

    Vancouver, British Columba, V5Z1M9

  • Victoria

    Victoria, British Columbia, BC V8R 1J8

Other trials in Canada

About this study

Official title: A Phase 3 Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of RBX2660 (Microbiota Suspension) for the Prevention of Clostridium Difficile Infection

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.

Read the detailed description

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.

Being tested
RBX2660, Placebo, Open label RBX2660 (only for confirmed CDI recurrence)
Keywords
C Difficile Colitis, Clostridium Difficile, CDI, C.Difficile Diarrhea, Fecal Transplant, Fecal Microbiota Transplant (FMT), Microbiota Restoration Therapy, Diarrhea, FMT, Microbial Suspension
Medical subject headings
Clostridium Infections, Enterocolitis, Pseudomembranous, Diarrhea

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 rectally administered microbiota suspension

  • PlaceboDrug

    Also called saline solution

    Placebo is normal saline solution administered rectally

  • Open label RBX2660 (only for confirmed CDI recurrence)Drug

    Also called microbiota suspension

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

Study groups in NCT03244644
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding
Receives: Drug: Placebo; Drug: Open label RBX2660 (only for confirmed CDI recurrence)
RBX2660ExperimentalRBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant
Receives: Drug: RBX2660; Drug: Open label RBX2660 (only for confirmed CDI recurrence)

What is being measured

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

  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.

    Measured: 8 weeks after completing the study treatment

Secondary outcomes (1)

  1. Sustained Clinical Response Through 6 Months After Blinded Treatment

    The rates of Sustained Clinical Response (i.e., the occurrence of new CDI infections from baseline through 6 months) was assessed by either the rate of new CDI infections after treatment success at 8 weeks (durability) or the frequency of total CDI infections from baseline through 6 months.

    Sustained Clinical Response was compared between the RBX2660 group and the control group using a chi-square test. Patients who exited prior to their 6-month follow-up were conservatively counted as a Treatment Failure

    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 posted9 Aug 2017
  2. Study start31 Jul 2017
  3. Primary completion2 Apr 2020
  4. Study completion3 Aug 2020

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
320 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03244644
Sponsor's protocol ID
2017-01
Status last verified
Jul 2024
First submitted
2 Aug 2017
Last updated
10 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 26031677

  • 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.

    PubMed 13592638

  • 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.

    PubMed 23530807

  • 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

  • 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

  • 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.

    PubMed 41115624

  • 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.

    PubMed 40672762

  • 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.

    PubMed 40552763

  • 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.

    PubMed 39172632

  • 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.

    PubMed 38236515

  • 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.

    PubMed 37564743

  • 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.

    PubMed 36287379

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RBX2660 and Open label RBX2660 (only for confirmed CDI recurrence) in people with Clostridium Difficile Infection (CDI), run by Rebiotix Inc. at 66 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 5 inclusion and 7 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 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 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. Some participants in this study may receive a placebo. 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 14 Aug 2023). 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?

Efficacy of RBX2660 Compared to Placebo Through 8 Weeks (time frame: 8 weeks after completing the 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 NCT03244644, which also lists 12 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 10 Jul 2024.

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