Clinical trial NCT01925417: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Clostridium Difficile Infection
Keywords: Clostridium difficile
C diff
Microbiota Restoration Therapy
MRT
microbiota suspension
CDI
CDAD
Fecal transplant
Fecal Microbiota Transplant
FMT
Diarrhea
Fecal bacteriotherapy
Lead sponsor: Rebiotix Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-19
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Incidence of Serious Adverse Events Through 56 Days After the Last Treatment With RBX2660
timeFrame: 56 days
Secondary outcomes:
measure: Long-term Safety
timeFrame: 6 months
measure: Absence of CDAD at 56 Days
timeFrame: 56 days
measure: Quality of Life (SF-36)
timeFrame: 60 days
measure: Post-treatment Hospitalization Data
timeFrame: 6 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Denver
country: United States
facility: Denver Health and University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Chicago
country: United States
facility: Edward Hines Jr VA Hospital (veterans only)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Fargo
country: United States
facility: Sanford Research/USD
state: North Dakota
Study officials:
affiliation: Veteran Administration Medical Center
name: Dimitri Drekonja, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.