ECOSPOR IV: An Open-Label Study Evaluating SER-109 in Recurrent Clostridioides Difficile Infection

ECOSPOR IV: An Open-Label Extension of Study SERES-012 and Open-Label Program for Evaluating SER-109 in Subjects With Recurrent Clostridioides Difficile Infection (RCDI)

Cohort 1: Subjects who had a Clostridioides difficile infection (CDI) recurrence in study SERES-012 within 8 weeks of receipt of study drug will be eligible. The purpose of this cohort is to assess safety and efficacy of SER-109 in reducing recurrence of CDI in adults who had a CDI recurrence within 8 weeks after receipt of SER-109 or Placebo in study SERES-012.

Cohort 2: Cohort 2 is an open-label program for subjects who were not part of SERES-012. The purpose of this cohort is to describe safety and tolerability of SER-109 in subjects 18 years of age or older with at least a first recurrence of CDI.

Study Overview

• Status: Completed
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Biological: SER-109

Detailed Description

Cohort 1 is an open-label extension of study SERES-012. Subjects who had a CDI recurrence in study SERES-012 within 8 weeks of receipt of study drug, have responded to a course of standard of care (SOC) antibiotic treatment, will receive an oral dose of SER-109. A treatment regimen of SER-109 is defined as an oral dose of SER-109 (4 capsules once daily) for 3 consecutive days.

Approximately 30 eligible subjects with recurrent CDI disease from study SERES-012 are expected to enroll. Screening for this study will begin at the Recurrence Visit of Study SERES-012.

Cohort 2 is an open-label program for subjects who were not part of SERES-012. Subjects 18 years of age or older who had one or more CDI recurrence and have responded to a course of antibiotic treatment will receive an oral dose of SER-109. The CDI recurrence must be confirmed by a positive C. difficile stool toxin or polymerase chain reaction (PCR) assay to confirm eligibility. A treatment regimen of SER-109 is defined as an oral dose of SER-109 (4 capsules once daily) for 3 consecutive days.

Approximately 200 eligible subjects with recurrent CDI disease are expected to enroll.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • (Investigator site)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • (Investigator site)
    • Victoria, British Columbia, Canada, V8R 1J8
      • (Investigator site)
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • (Investigator site)
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • (Investigator site)
    • North Bay, Ontario, Canada, P1B 2H3
      • (Investigator site)
    • Scarborough, Ontario, Canada, M1P 2T7
      • (Investigator site)
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7Y8
      • (Investigator site)
    • Québec, Quebec, Canada, G2J 0C4
      • (Investigator site)
    • Sainte-Foy, Quebec, Canada, G1W 4R4
      • (Investigator site)
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • (Investigator site)
  • Arizona
    • Sun City West, Arizona, United States, 85375
      • (Investigator site)
  • California
    • Mather, California, United States, 95655
      • (Investigator site)
    • Mountain View, California, United States, 94040
      • (Investigator site)
    • Murrieta, California, United States, 92563
      • (Investigator site)
    • Northridge, California, United States, 91324
      • (Investigator site)
    • Sacramento, California, United States, 95817
      • (Investigator site)
    • San Bernardino, California, United States, 92408
      • (Investigator site)
    • San Diego, California, United States, 92123
      • (Investigator site)
    • San Dimas, California, United States, 91773
      • (Investigator site)
    • Simi Valley, California, United States, 93065
      • (Investigator site)
    • Thousand Oaks, California, United States, 91360
      • (Investigator site)
  • Florida
    • Clearwater, Florida, United States, 33756
      • (Investigator site)
    • Clearwater, Florida, United States, 33761
      • (Investigator site)
    • DeLand, Florida, United States, 32720
      • (Investigator site)
    • Hialeah, Florida, United States, 33016
      • (Investigator site)
    • Homestead, Florida, United States, 33032
      • (Investigator site)
    • Jacksonville, Florida, United States, 32256
      • (Investigator site)
    • Miami, Florida, United States, 33125
      • (Investigator site)
    • Miami, Florida, United States, 33126
      • (Investigator site)
    • Miami, Florida, United States, 33144
      • (Investigator site)
    • Miami, Florida, United States, 33155
      • (Investigator site)
    • Miami, Florida, United States, 33165
      • (Investigator site)
    • Miami, Florida, United States, 33175
      • (Investigator site)
    • Miami Lakes, Florida, United States, 33014
      • (Investigator site)
    • Naples, Florida, United States, 34102
      • (Investigator site)
    • Orlando, Florida, United States, 32819
      • (Investigator site)
    • Pembroke Pines, Florida, United States, 33024
      • (Investigator site)
    • Pembroke Pines, Florida, United States, 33026
      • (Investigator site)
    • Port Orange, Florida, United States, 32127
      • (Investigator site)
  • Georgia
    • Athens, Georgia, United States, 30607
      • (Investigator site)
    • Atlanta, Georgia, United States, 30322
      • (Investigator site)
    • Decatur, Georgia, United States, 30033
      • (Investigator site)
    • Marietta, Georgia, United States, 30060
      • (Investigator site)
    • Morrow, Georgia, United States, 30260
      • (Investigator site)
  • Idaho
    • Boise, Idaho, United States, 83706
      • (Investigator site)
    • Idaho Falls, Idaho, United States, 83404
      • (Investigator site)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • (Investigator site)
    • Oak Lawn, Illinois, United States, 60453
      • (Investigator site)
    • Springfield, Illinois, United States, 62703
      • (Investigator site)
  • Indiana
    • Evansville, Indiana, United States, 47714
      • (Investigator site)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • (Investigator site)
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • (Investigator site)
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • (Investigator site)
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • (Investigator site)
    • Chevy Chase, Maryland, United States, 20815
      • (Investigator site)
    • Glen Burnie, Maryland, United States, 21061
      • (Investigator site)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • (Investigator site)
    • Framingham, Massachusetts, United States, 01702
      • (Investigator site)
    • North Dartmouth, Massachusetts, United States, 02747
      • (Investigator site)
    • Weymouth, Massachusetts, United States, 02190
      • (Investigator site)
    • Worcester, Massachusetts, United States, 01655
      • (Investigator site)
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • (Investigator site)
    • Detroit, Michigan, United States, 48202
      • (Investigator site)
    • Flint, Michigan, United States, 48504
      • (Investigator site)
    • Royal Oak, Michigan, United States, 48073
      • (Investigator site)
    • Wyoming, Michigan, United States, 49519
      • (Investigator site)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • (Investigator site)
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • (Investigator site)
  • Montana
    • Butte, Montana, United States, 59701
      • (Investigator site)
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • (Investigator site)
    • Neptune, New Jersey, United States, 07754
      • (Investigator site)
  • New York
    • Buffalo, New York, United States, 14215
      • (Investigator site)
    • New York, New York, United States, 10279
      • (Investigator site)
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • (Investigator site)
    • Greenville, North Carolina, United States, 27834
      • (Investigator site)
    • Jacksonville, North Carolina, United States, 28546
      • (Investigator site)
    • Kinston, North Carolina, United States, 28501
      • (Investigator site)
  • Ohio
    • Akron, Ohio, United States, 44304
      • (Investigator site)
    • Centerville, Ohio, United States, 45459
      • (Investigator site)
    • Cincinnati, Ohio, United States, 45219
      • (Investigator site)
    • Cleveland, Ohio, United States, 44195
      • (Investigator site)
    • Mentor, Ohio, United States, 44060
      • (Investigator site)
    • Toledo, Ohio, United States, 43617
      • (Investigator site)
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • (Investigator site)
    • Harrisburg, Pennsylvania, United States, 17110
      • (Investigator site)
    • Pittsburgh, Pennsylvania, United States, 15213
      • (Investigator site)
    • Sayre, Pennsylvania, United States, 18840
      • (Investigator site)
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • (Investigator site)
  • Tennessee
    • Union City, Tennessee, United States, 38261
      • (Investigator site)
  • Texas
    • Cypress, Texas, United States, 77429
      • (Investigator site)
    • Garland, Texas, United States, 75044
      • (Investigator site)
    • Houston, Texas, United States, 77024
      • (Investigator site)
    • Houston, Texas, United States, 77025
      • (Investigator site)
    • Houston, Texas, United States, 77057
      • (Investigator site)
    • Houston, Texas, United States, 77084
      • (Investigator site)
    • McKinney, Texas, United States, 75071
      • (Investigator site)
    • Pasadena, Texas, United States, 77505
      • (Investigator site)
    • San Antonio, Texas, United States, 78229
      • (Investigator site)
    • Southlake, Texas, United States, 76092
      • (Investigator site)
    • Spring, Texas, United States, 77379
      • (Investigator site)
  • Utah
    • Ogden, Utah, United States, 84403
      • (Investigator site)
    • Riverton, Utah, United States, 84065
      • (Investigator site)
    • Salt Lake City, Utah, United States, 84114
      • (Investigator site)
  • Washington
    • Spokane, Washington, United States, 99202
      • (Investigator site)
    • Tacoma, Washington, United States, 98405
      • (Investigator site)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • (Investigator site)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Cohort 1 Main Inclusion Criteria:

1. Previously enrolled in Study SERES-012, had CDI recurrence within 8 weeks after receipt of a treatment regimen of SER-109 or placebo
2. 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.
3. The CDI recurrence in Study SERES-012 must have met the protocol definition of ≥ 3 unformed stools per day over 2 consecutive days, a positive C. difficile stool toxin assay, and the requirement of CDI SOC antibiotic therapy, and an adequate clinical response following antibiotic therapy (<3 unformed stools in 24 hours for 2 or more consecutive days).

Cohort 1 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/mm^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) in the past 3 months.

Cohort 2 Main Inclusion Criteria:

1. Subjects 18 years of age or older who had one or more CDI recurrence (as confirmed by a C. difficile stool toxin or PCR test) and have responded to a course of antibiotic treatment.
2. 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.

Cohort 2 Main Exclusion Criteria:

(all Cohort 1 exclusion criteria [#1-8 above] plus the below addition criterion)

9. Previously enrolled in a Seres Therapeutics clinical study. An exception is made for subjects who screened in SERES-012 who did not receive SER-109 and did not previously roll-over to SERES-013.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SER-109; Received oral dose of SER-109	Biological: SER-109; SER-109, an oral, biologically derived, live microbiome therapeutic that comprises purified bacterial spores; Other Names: Firmicutes spores

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Recurrence of CDI and Sustained Clinical Response	Cohort 1: Recurrence of CDI up to 8 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 Weeks after treatment.	Up to Week 8
Cohort 2: Recurrence of CDI and Sustained Clinical Response	Cohort 2: Recurrence of CDI up to 8 and 12 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 and 12 Weeks after treatment.	Up to Weeks 8 and 12

Collaborators and Investigators

• Sponsor: Seres Therapeutics, Inc.
• Investigators: Study Director: Elaine Wang, MD, Seres Therapeutics, Inc.

Publications and helpful links

General Publications

• Buske C, Dimopoulos MA, Grunenberg A, Kastritis E, Tomowiak C, Mahe B, Troussard X, Hajek R, Viardot A, Tournilhac O, Aurran T, Lepretre S, Zerazhi H, Hivert B, Leblond V, de Guibert S, Brandefors L, Garcia-Sanz R, Gomes da Silva M, Kimby E, Schmelzle B, Kaszynski D, Dreyhaupt J, Muche R, Morel P. Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenstrom's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenstrom's Macroglobulinemia. J Clin Oncol. 2023 Feb 10:JCO2201805. doi: 10.1200/JCO.22.01805. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Actual): April 29, 2022
• Study Completion (Actual): April 29, 2022

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 8, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Communicable Diseases; Gram-Positive Bacterial Infections; Clostridioides infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections
• Other Study ID Numbers: SERES-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No