Clinical trial NCT03183128: ECOSPOR III - SER-109 Versus Placebo in the Treatment of Adults With Recurrent Clostridium Difficile Infection
Official title: A Phase 3 Multicenter, RandomizeEd, Double Blind, Placebo COntrolled, Parallel Group Study to Evaluate the Safety, Tolerability, & Efficacy of SER-109 vs. Placebo to Reduce Recurrence of ClOstRidium Difficile Infection (CDI) in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Infection
Lead sponsor: Seres Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-09
Enrollment: 182
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: Subjects will receive an oral dose of SER-109 in 4 capsules once daily for 3 consecutive days in Treatment Group I or matching placebo once daily for 3 consecutive days in Treatment Group II. The purpose of this study is to demonstrate the superiority of SER-109 vs placebo to reduce recurrence of CDI as determined by a toxin assay in adults up to 8 weeks after initiation of treatment.

Detailed description: ECOSPOR III is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the safety, tolerability, and efficacy of SER-109 versus placebo in adult subjects 18 years of age or older with recurrent CDI, defined as: a history of ≥ 3 CDI episodes within 12 months, inclusive of the current episode. This study is designed to demonstrate the superiority of SER-109 versus placebo to reduce recurrence of Clostridium difficile infection (CDI) in adults who have received antibacterial drug treatment for recurrent CDI (RCDI), based on the proportion of subjects experiencing a CDI recurrence requiring antibiotic treatment up to 8 weeks after initiation of treatment. Approximately 188 subjects with a history of CDI, diarrhea and a positive C. difficile toxin test result on a stool sample, who have responded to standard-of-care (SOC) antibiotic treatment will be enrolled. Subjects will be randomly assigned, in a 1:1 ratio, to 1 of 2 treatment groups (Treatment Group I \[SER-109\] or Treatment Group II \[Placebo\]) and stratified by age (\<65 years; ≥65 years), as well as antibiotic regimen for the qualifying episode (vancomycin; fidaxomicin).

Subjects will receive an oral dose of SER-109 in 4 capsules once daily for 3 consecutive days in Treatment Group I or matching placebo once daily for 3 consecutive days in Treatment Group II.

Subjects with confirmed CDI recurrence, as defined in the Protocol, up to 8 weeks after administration of SER-109 or placebo treatment, may be eligible to enroll in the open-label SER-109 extension study (Study SERES-013).

Eligibility criteria: Main Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-specific procedure or treatment. The subject or their legally authorized representative must be able to provide written informed consent and understand the potential risks and benefits from study enrollment and treatment.
2. Male or female subject ≥ 18 years of age.
3. A qualifying episode of CDI as defined by:

   1. ≥ 3 unformed stools per day for 2 consecutive days
   2. A positive C. difficile stool toxin assay.
   3. The requirement of CDI SOC antibiotic therapy (defined as 10 to 21 days of treatment with vancomycin \[125 mg QID\] and/or fidaxomicin \[200 mg BID\]).
   4. An adequate clinical response following SOC antibiotic therapy, defined as (\<3 unformed stools in 24 hours) for 2 or more consecutive days before randomization.

Main Exclusion Criteria:

1. Female subjects who are pregnant, breastfeeding, lactating, or planning to become pregnant during the study.
2. Known or suspected toxic megacolon and/or known small bowel ileus.
3. Admitted to or expected to be admitted to an intensive care unit for medical reasons (not just boarding). Note: nursing homes, rehabilitation, assisted living centers and acute care hospitals are acceptable.
4. Absolute neutrophil count of \<500 cells/ml\^3
5. Major gastrointestinal surgery (e.g. significant bowel resection or diversion) within 3 months before enrollment (this does not include appendectomy or cholecystectomy), or any history of total colectomy or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, i.e., restrictive procedures such as banding, are permitted).
6. History of active inflammatory bowel disease (ulcerative colitis, Crohn's disease, microscopic colitis) with diarrhea believed to be caused by active inflammatory bowel disease in the past 3 months.
7. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with the study medical monitor).
8. Any history of fecal microbiota transplantation (FMT) within the previous 3 months.

Primary outcomes:
measure: Recurrence of CDI up to 8 Weeks
timeFrame: Up to Week 8
Secondary outcomes:
measure: Recurrence of CDI up to 4, 12 and 24 Weeks
timeFrame: Up to 4, 12 and 24 weeks after treatment
Other outcomes:
Locations:
city: North Little Rock
country: United States
facility: (Investigator site)
state: Arkansas
city: Mather
country: United States
facility: (Investigator site)
state: California
city: Mountain View
country: United States
facility: (Investigator site)
state: California
city: Northridge
country: United States
facility: (Investigator site)
state: California
city: Sacramento
country: United States
facility: (Investigator site)
state: California
city: Simi Valley
country: United States
facility: (Investigator site)
state: California
city: Upland
country: United States
facility: (Investigator site)
state: California
city: Hamden
country: United States
facility: (Investigator site)
state: Connecticut
city: Washington
country: United States
facility: (Investigator site)
state: District of Columbia
city: Jacksonville
country: United States
facility: (Investigator site)
state: Florida
city: Miami
country: United States
facility: (Investigator site)
state: Florida
city: Miami
country: United States
facility: (Investigator site)
state: Florida
city: Pembroke Pines
country: United States
facility: (Investigator site)
state: Florida
city: Pembroke Pines
country: United States
facility: (Investigator site)
state: Florida
city: Athens
country: United States
facility: (Investigator site)
state: Georgia
city: Atlanta
country: United States
facility: (Investigator site)
state: Georgia
city: Marietta
country: United States
facility: (Investigator site)
state: Georgia
city: Riverdale
country: United States
facility: (Investigator site)
state: Georgia
city: Sandy Springs
country: United States
facility: (Investigator site)
state: Georgia
city: Idaho Falls
country: United States
facility: (Investigator site)
state: Idaho
city: Springfield
country: United States
facility: (Investigator site)
state: Illinois
city: Evansville
country: United States
facility: (Investigator site)
state: Indiana
city: Jeffersonville
country: United States
facility: (Investigator site)
state: Indiana
city: Iowa City
country: United States
facility: (Investigator site)
state: Iowa
city: Kansas City
country: United States
facility: (Investigator site)
state: Kansas
city: New Orleans
country: United States
facility: (Investigator site)
state: Louisiana
city: Annapolis
country: United States
facility: (Investigator site)
state: Maryland
city: Chevy Chase
country: United States
facility: (Investigator site)
state: Maryland
city: Boston
country: United States
facility: (Investigator site)
state: Massachusetts
city: Worcester
country: United States
facility: (Investigator site)
state: Massachusetts
city: Detroit
country: United States
facility: (Investigator site)
state: Michigan
city: Royal Oak
country: United States
facility: (Investigator site)
state: Michigan
city: Saint Louis
country: United States
facility: (Investigator site)
state: Missouri
city: Butte
country: United States
facility: (Investigator site)
state: Montana
city: Las Vegas
country: United States
facility: (Investigator site)
state: Nevada
city: Buffalo
country: United States
facility: (Investigator site)
state: New York
city: Greenville
country: United States
facility: (Investigator site)
state: North Carolina
city: Kinston
country: United States
facility: (Investigator site)
state: North Carolina
city: Raleigh
country: United States
facility: (Investigator site)
state: North Carolina
city: Centerville
country: United States
facility: (Investigator site)
state: Ohio
city: Cleveland
country: United States
facility: (Investigator site)
state: Ohio
city: Columbus
country: United States
facility: (Investigator site)
state: Ohio
city: Pittsburgh
country: United States
facility: (Investigator site)
state: Pennsylvania
city: Sayre
country: United States
facility: (Investigator site)
state: Pennsylvania
city: Houston
country: United States
facility: (Investigator site)
state: Texas
city: San Antonio
country: United States
facility: (Investigator site)
state: Texas
city: Southlake
country: United States
facility: (Investigator site)
state: Texas
city: Bountiful
country: United States
facility: (Investigator site)
state: Utah
city: Riverton
country: United States
facility: (Investigator site)
state: Utah
city: Charlottesville
country: United States
facility: (Investigator site)
state: Virginia
city: Reston
country: United States
facility: (Investigator site)
state: Virginia
city: Calgary
country: Canada
facility: (Investigator site)
state: Alberta
city: Vancouver
country: Canada
facility: (Investigator site)
state: British Columbia
city: Victoria
country: Canada
facility: (Investigator site)
state: British Columbia
city: London
country: Canada
facility: (Investigator site)
state: Ontario
city: Chicoutimi
country: Canada
facility: (Investigator site)
state: Quebec
Study officials:
affiliation: Seres Therapeutics, Inc.
name: Lisa von Moltke, MD
role: STUDY_DIRECTOR
References:
citation: Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, Korman LY, Ford CB, Litcofsky KD, Lombardo MJ, Wortman JR, Wu H, Aunins JG, McChalicher CWJ, Winkler JA, McGovern BH, Trucksis M, Henn MR, von Moltke L. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022 Jan 20;386(3):220-229. doi: 10.1056/NEJMoa2106516.