Microbiota Restoration Therapy for Recurrent Clostridium Difficile-associated Diarrhea (PUNCH CD)

• ClinicalTrials.gov Identifier: NCT01925417
• Recruitment Status: Completed
• First Posted: August 19, 2013
• Results First Posted: July 1, 2015
• Last Update Posted: November 13, 2019
• Sponsor: Rebiotix Inc.
• Information provided by (Responsible Party): Rebiotix Inc.

Tracking Information

• First Submitted Date: August 15, 2013
• First Posted Date: August 19, 2013
• Results First Submitted Date: May 28, 2015
• Results First Posted Date: July 1, 2015
• Last Update Posted Date: November 13, 2019
• Study Start Date: August 2013
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2015)

Incidence of Serious Adverse Events Through 56 Days After the Last Treatment With RBX2660 [ Time Frame: 56 days ]

Safety will be assessed by evaluating the incidence of serious adverse events through 56 days after the last treatment with RBX2660.

Original Primary Outcome Measures (submitted: August 15, 2013)

Safety [ Time Frame: 56 days ]

Safety will be assessed by evaluating the incidence, severity, and relatedness of serious adverse events through 56 days after the last treatment with RBX2660.

Current Secondary Outcome Measures (submitted: September 7, 2018)

• Long-term Safety [ Time Frame: 6 months ]
  The incidence of serious adverse events will be assessed through 6 months after the last treatment with RBX2660.
• Absence of CDAD at 56 Days [ Time Frame: 56 days ]
  Number of participants who were determined to be free of CDAD at Day 56 after receiving their last dose of RBX2660.
• Quality of Life (SF-36) [ Time Frame: 60 days ]
  Quality of Life (SF-36) will be assessed by comparing the subject's baseline quality of life score to his/her scores obtained at the 7-, 30- and 60-day follow-up visits. The scale is from 0-100, with higher scores meaning better outcomes.
• Post-treatment Hospitalization Data [ Time Frame: 6 months ]
  number of ICU days was collected for subjects who received RBX2660 and who were subsequently hospitalized for recurrent CDAD treatment.

Original Secondary Outcome Measures (submitted: August 15, 2013)

• Long-term Safety [ Time Frame: 6 months ]
  Serious adverse events will be assessed through 6 months after the last treatment with RBX2660.
• Efficacy [ Time Frame: 56 days ]
  Absence or presence of CDAD at Day 56 after receiving RBX2660. Subjects who reoccur before Day 56 may receive a second treatment with RBX2660 within 10 days of recurrence.
• Quality of Life [ Time Frame: 60 days ]
  Quality of life will be assessed by comparing the subject's baseline quality of life score to his/her scores obtained at the 7-, 30- and 60-day follow-up visits.
• Post-treatment Hospitalization Data [ Time Frame: 6 months ]
  Hospitalization cost, number of ICU days, and length of stay data will be collected for subjects who receive RBX2660 and who are subsequently hospitalized for recurrent CDAD treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Microbiota Restoration Therapy for Recurrent Clostridium Difficile-associated Diarrhea
• Official Title: A Phase 2 Open-label Clinical Trial Demonstrating the Safety of RBX2660 Microbiota Suspension for the Treatment of Recurrent Clostridium Difficile-associated Diarrhea (CDAD): the PUNCH CD Study
• Brief Summary: This study will assess the safety of a new biologic drug, RBX2660 (microbiota suspension) as a treatment for recurrent Clostridium difficile-associated diarrhea (CDAD), which is the primary symptom of recurrent Clostridium difficile infection. All eligible subjects will receive RBX2660.
• Detailed Description: This is the first study of a microbiota suspension derived from intestinal microbes. The primary assessments for this open label, multi-center study are (i) occurrence of product-related adverse events and (ii) resolution of CDAD at 56 days after administration of RBX2660. Subjects will also be assessed for time to CDAD recurrence, quality of life changes, and number of hospitalizations and length of stay for recurrent CDAD. Study visits will be at 7, 30, and 60 days after RBX2660 administration with additional follow-up at 3 and 6 months post treatment. Patients who have had at least two recurrences of CDAD after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDAD resulting in hospitalization may be eligible for the study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent Clostridium Difficile Infection
• Intervention: Biological: RBX2660 (microbiota suspension)

Study Arms

Experimental: RBX2660 (microbiota suspension)

enema-based delivery of RBX2660

Intervention: Biological: RBX2660 (microbiota suspension)

Publications *

• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
• Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011 Nov;53(10):994-1002. doi: 10.1093/cid/cir632.
• Rohlke F, Stollman N. Fecal microbiota transplantation in relapsing Clostridium difficile infection. Therap Adv Gastroenterol. 2012 Nov;5(6):403-20. doi: 10.1177/1756283X12453637.
• Langdon A, Schwartz DJ, Bulow C, Sun X, Hink T, Reske KA, Jones C, Burnham CD, Dubberke ER, Dantas G; CDC Prevention Epicenter Program. Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study. Genome Med. 2021 Feb 16;13(1):28. doi: 10.1186/s13073-021-00843-9.
• Orenstein R, Dubberke E, Hardi R, Ray A, Mullane K, Pardi DS, Ramesh MS; PUNCH CD Investigators. Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study. Clin Infect Dis. 2016 Mar 1;62(5):596-602. doi: 10.1093/cid/civ938. Epub 2015 Nov 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2015): 34
• Original Estimated Enrollment (submitted: August 15, 2013): 40
• Actual Study Completion Date: July 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ≥ 18 years
• Medical record documentation of CDAD either: a) at least two recurrences after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or b) have had at least two episodes of severe CDAD resulting in hospitalization.
• Willing and able to have an enema(s).
• Already taking or will start a course of oral antibiotics for CDAD symptoms for 10-14 days, including at least seven days of oral vancomycin.
• Willing and able to complete the required subject diary.

Exclusion Criteria:

• Continued (uncontrolled) CDAD after completing a 10-14 day course of oral antibiotics.
• Requires antibiotic therapy for a condition other than CDAD.
• Previous fecal transplant prior to study enrollment.
• History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
• History of irritable bowel syndrome (IBS).
• History of chronic diarrhea.
• History of celiac disease.
• History of cirrhosis of the liver or ascites.
• Disease symptoms caused by a confirmed intestinal pathogen other than Clostridium difficile.
• Has a colostomy.
• Intraabdominal surgery within the last 60 days.
• Evidence of active, severe colitis.
• History of short gut syndrome or motility disorders.
• Requires the regular use of medications that affect bowel motility (e.g., metoclopramide, narcotics, loperamide).
• Planned therapy in the next 3 months that may cause diarrhea (e.g., chemotherapy).
• Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
• Life expectancy of < 12 months.
• Compromised immune system, e.g., HIV infection (any CD4 count); AIDS-defining diagnosis or CD4 <200/mm3; inherited/primary immune disorders; immunodeficient or immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy; or current or recent (< 90 days) treatment with immunosuppressant medications.
• Taking steroids (≥ 20 mg a day) or is expected to be on steroids for more than 30 days after enrollment.
• Neutropenia (white blood cell count <1000 cells/µL).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01925417
• Other Study ID Numbers: 2013-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rebiotix Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Rebiotix Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Dimitri Drekonja, MD; Veteran Administration Medical Center

• PRS Account: Rebiotix Inc.
• Verification Date: September 2018