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A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02618187
Recruitment Status : Completed
First Posted : December 1, 2015
Results First Posted : June 20, 2019
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Seres Therapeutics, Inc.

Brief Summary:
A Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects with Mild-to-Moderate Ulcerative Colitis.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: SER-287 Drug: Placebo Drug: Placebo Pre-Treat Drug: Vancomycin Pre-Treat Phase 1

Detailed Description:
This is a Phase 1b multicenter, randomized, double-blind, placebo-controlled multiple dose study designed to evaluate the safety and tolerability of SER-287, and to evaluate the microbiome alterations and pharmacodynamics associated with two dosing regimens of SER-287 in adult subjects with active mild-to-moderate ulcerative colitis (UC).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1B Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis
Actual Study Start Date : January 13, 2016
Actual Primary Completion Date : December 6, 2017
Actual Study Completion Date : January 26, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Weekly SER-287, after Placebo Pre-Treat.
Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Drug: SER-287
Other Name: Eubacterial Spores, Purified Suspension, Encapsulated

Drug: Placebo Pre-Treat
Placebo Comparator: Daily placebo, after Placebo Pre-Treat.
Placebo pre-treatment, followed by once daily placebo for 8 weeks
Drug: Placebo
Drug: Placebo Pre-Treat
Experimental: Daily SER-287, after Vanco. Pre-Treat.
Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks
Drug: SER-287
Other Name: Eubacterial Spores, Purified Suspension, Encapsulated

Drug: Vancomycin Pre-Treat
Experimental: Weekly SER-287, after Vanco. Pre-Treat.
Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Drug: SER-287
Other Name: Eubacterial Spores, Purified Suspension, Encapsulated

Drug: Vancomycin Pre-Treat



Primary Outcome Measures :
  1. Safety and Tolerability of SER-287 [ Time Frame: Day 246 ]
    Treatment-Emergent Adverse Events Incidence by Treatment, System Organ Class and Preferred Term. The treatment period with SER-287 was eight weeks. All AEs were collected from the date of Informed Consent (up to 17 days of Screening) through Day 92 of the study. All SAEs were collected from the date of Informed Consent through Day 246 of the study.

  2. Composition of the Intestinal Microbiome [ Time Frame: Baseline and 8 weeks ]
    Changes in the composition of the microbiome were characterized by whole metagenomic sequencing (WMS) of subjects' stool samples. Changes in the composition of the microbiome were measured by quantifying the number of unique types of spore-forming bacteria detected in subjects' stool samples after eight weeks of induction treatment versus baseline.

  3. Engraftment of SER-287 Bacteria in All Treatment Arms [ Time Frame: Baseline and 8 weeks ]
    The stool microbiomes of SERES-101 subjects, before and after treatment with SER-287, were characterized using whole metagenomic sequencing (WMS). SER-287 drug product was also characterized using WMS. Microbiome engraftment was assessed by the number of spore-forming species in the drug product lots that were also detected in subjects' post-treatment fecal samples but not detected at baseline.


Secondary Outcome Measures :
  1. Clinical Remission [ Time Frame: 8 weeks ]

    Defined as a Total Modified Mayo Score <= 2 and an endoscopic subscore <= 1.

    The Total Modified Mayo Score is a measure of UC disease activity which ranges from 0 to 12 points and consists of four subscores (stool frequency, rectal bleeding, endoscopy, and physician global assessment), each graded from 0 to 3, with higher scores indicating more severe disease. The four components are summed together for a composite score, with a higher overall score indicating more severe disease (0 = no disease; 12 = worst disease). The Modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1.


  2. Endoscopic Improvement [ Time Frame: 8 weeks ]
    Defined as a decrease in endoscopic subscore >= 1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic and pathologic criteria (preferably confirmed by colonoscopy and pathology records within last 2 years or if unavailable, will need approval by medical monitor) Active mild-moderate UC as determined by sigmoidoscopy within approximately 3 days of randomization to study

Exclusion Criteria:

  1. Fever > 38.3°C
  2. Known or suspected toxic megacolon and/or known small bowel ileus
  3. Known history of Crohn's disease
  4. Subjects with serum albumin <2.5 g/dL at baseline
  5. CMV polymerase chain reaction (PCR) positive from blood plasma at screening
  6. Known stool studies positive for ova and/or parasites or stool culture within the 30 days before enrollment
  7. Subjects on cyclosporine or triple immunosuppression, Triple immunosuppression will include any three of the following classes of drugs taken in combination: steroids (i.e., prednisone/budesonide/budesonide MMX), immunosuppressant (i.e., methotrexate/azathioprine/6-mercaptopurine), and/or other immunosuppressant (i.e., tacrolimus, cellcept).
  8. Biologic medication (infliximab/ adalimumab/ golimumab/ certolizumab/vedolizumab/ustekinumab/natalizumab) use within 3 months prior to screening
  9. Known active malignancy except for basal cell skin cancer, squamous cell skin cancer
  10. Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery (excluding cholecystectomy, appendectomy)
  11. Subjects with known history of celiac disease or gluten enteropathy
  12. Subjects with Clostridium difficile positive stool at Screening Visit
  13. Antibiotic use within the prior 1 month before randomization
  14. Expected to receive antibiotics within 8 weeks of signing the Informed Consent Form (ICF) (i.e., for planned/anticipated procedure)
  15. Received an investigational drug within 1 month before study entry
  16. Received an investigational antibody or vaccine within 3 months before study entry
  17. Previously enrolled in a SER-109/SER-287 study
  18. Received an FMT within the last 6 months
  19. Subjects with anatomic or medical contraindications to flexible sigmoidoscopy, including but not necessarily limited to toxic megacolon, gastrointestinal (GI) fistulas, immediate post-operative status from abdominal surgery, severe coagulopathy, large or symptomatic abdominal aortic aneurysm, or any subject where study physician deems subject at significant risk of complications of flexible sigmoidoscopy
  20. Unable to stop steroid enemas or suppositories or mesalamine enemas or suppositories before screening visit
  21. Unable to stop opiate treatment unless on a stable dose and no increase in dose planned for the duration of the study
  22. Unable to stop probiotics before screening visit
  23. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with medical monitor)
  24. Known allergy or intolerance to oral vancomycin

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02618187


Locations
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United States, Massachusetts
Community Clinical Research Network
Marlborough, Massachusetts, United States, 01752
Sponsors and Collaborators
Seres Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Seres Therapeutics, Inc.:
Study Protocol  [PDF] October 10, 2016


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Responsible Party: Seres Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02618187     History of Changes
Other Study ID Numbers: SERES-101
First Posted: December 1, 2015    Key Record Dates
Results First Posted: June 20, 2019
Last Update Posted: June 20, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents