Clinical trial NCT03244644: Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Infection (CDI)
Keywords: C Difficile Colitis
Clostridium Difficile
CDI
C.Difficile Diarrhea
Fecal Transplant
Fecal Microbiota Transplant (FMT)
Microbiota Restoration Therapy
Diarrhea
FMT
Microbial Suspension
Lead sponsor: Rebiotix Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-09
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

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.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years old.
2. 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.
3. A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.
4. Is currently taking or was just prescribed antibiotics to control CDI related diarrhea at the time of enrollment.

\[Note: Subject's CDI diarrhea must be controlled (\<3 unformed/loose stools/day) while taking this course of antibiotics\]

Exclusion Criteria:

1. Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.
2. Previous fecal transplant
3. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
4. Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.
5. Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (\< 90 days) treatment with chemotherapy)
6. An absolute neutrophil count of \<1000 cells/µL during screening.
7. Pregnant, breastfeeding, or intends to become pregnant during study participation.

Primary outcomes:
measure: Efficacy of RBX2660 Compared to Placebo Through 8 Weeks
timeFrame: 8 weeks after completing the study treatment
Secondary outcomes:
measure: Sustained Clinical Response Through 6 Months After Blinded Treatment
timeFrame: 6 months after completing the study treatment
Other outcomes:
Locations:
city: Athens
country: United States
facility: Athens
state: Alabama
city: Dothan
country: United States
facility: Dothan
state: Alabama
city: Phoenix
country: United States
facility: Phoenix
state: Arizona
city: North Little Rock
country: United States
facility: North Little Rock
state: Arkansas
city: Lancaster
country: United States
facility: Lancaster
state: California
city: Los Angeles
country: United States
facility: Los Angeles
state: California
city: Oxnard
country: United States
facility: Oxnard
state: California
city: Sacramento
country: United States
facility: Sacramento
state: California
city: Aurora
country: United States
facility: Aurora
state: Colorado
city: Hamden
country: United States
facility: Hamden
state: Connecticut
city: Gainesville
country: United States
facility: Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Port Orange
country: United States
facility: Port Orange
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Idaho Falls
country: United States
facility: Idaho Falls
state: Idaho
city: Gurnee
country: United States
facility: Gurnee
state: Illinois
city: Highland Park
country: United States
facility: Highland Park
state: Illinois
city: Maywood
country: United States
facility: Maywood
state: Illinois
city: Lafayette
country: United States
facility: Lafayette
state: Indiana
city: Topeka
country: United States
facility: Topeka
state: Kansas
city: Wichita
country: United States
facility: Wichita
state: Kansas
city: Lexington
country: United States
facility: Lexington
state: Kentucky
city: New Orleans
country: United States
facility: New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Shreveport
state: Louisiana
city: Boston
country: United States
facility: Boston
state: Massachusetts
city: Detroit
country: United States
facility: Detroit
state: Michigan
city: Plymouth
country: United States
facility: Plymouth
state: Minnesota
city: Rochester
country: United States
facility: Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis
state: Missouri
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
city: Teaneck
country: United States
facility: Teaneck
state: New Jersey
city: New York
country: United States
facility: New York
state: New York
city: North Massapequa
country: United States
facility: North Massapequa
state: New York
city: Rochester
country: United States
facility: Rochester
state: New York
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Greenville
country: United States
facility: Greenville
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington
state: North Carolina
city: Fargo
country: United States
facility: Fargo
state: North Dakota
city: Toledo
country: United States
facility: Toledo
state: Ohio
city: Portland
country: United States
facility: Portland
state: Oregon
city: Flourtown
country: United States
facility: Flourtown
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Uniontown
country: United States
facility: Uniontown
state: Pennsylvania
city: Wyomissing
country: United States
facility: Wyomissing
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City
state: South Dakota
city: Hixson
country: United States
facility: Hixson
state: Tennessee
city: Dallas
country: United States
facility: Dallas
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: West Jordan
country: United States
facility: West Jordan
state: Utah
city: Springfield
country: United States
facility: Springfield
state: Virginia
city: Winchester
country: United States
facility: Winchester
state: Virginia
city: Seattle
country: United States
facility: Seattle
state: Washington
city: Madison
country: United States
facility: Madison
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield
state: Wisconsin
city: Calgary
country: Canada
facility: Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Edmonton
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver
state: British Columba
city: Victoria
country: Canada
facility: Victoria
state: British Columbia
city: Fredericton
country: Canada
facility: Fredericton
state: New Brunswick
city: Moncton
country: Canada
facility: Moncton
state: New Brunswick
Study officials:
affiliation: Wayne State University
name: Teena Chopra, M.D., M.P.H.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.