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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

Primary Purpose

Ulcerative Colitis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SER-287
Placebo
Placebo Pre-Treat
Vancomycin Pre-Treat
Sponsored by
Seres Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    -

Sites / Locations

  • Community Clinical Research Network

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Weekly SER-287, after Placebo Pre-Treat.

Daily placebo, after Placebo Pre-Treat.

Daily SER-287, after Vanco. Pre-Treat.

Weekly SER-287, after Vanco. Pre-Treat.

Arm Description

Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks

Placebo pre-treatment, followed by once daily placebo for 8 weeks

Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks

Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks

Outcomes

Primary Outcome Measures

Safety and Tolerability of SER-287
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.
Composition of the Intestinal Microbiome
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.
Engraftment of SER-287 Bacteria in All Treatment Arms
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

Clinical Remission
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.
Endoscopic Improvement
Defined as a decrease in endoscopic subscore >= 1

Full Information

First Posted
November 20, 2015
Last Updated
March 20, 2019
Sponsor
Seres Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02618187
Brief Title
A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
January 13, 2016 (Actual)
Primary Completion Date
December 6, 2017 (Actual)
Study Completion Date
January 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seres Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Weekly SER-287, after Placebo Pre-Treat.
Arm Type
Experimental
Arm Description
Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Arm Title
Daily placebo, after Placebo Pre-Treat.
Arm Type
Placebo Comparator
Arm Description
Placebo pre-treatment, followed by once daily placebo for 8 weeks
Arm Title
Daily SER-287, after Vanco. Pre-Treat.
Arm Type
Experimental
Arm Description
Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks
Arm Title
Weekly SER-287, after Vanco. Pre-Treat.
Arm Type
Experimental
Arm Description
Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Intervention Type
Drug
Intervention Name(s)
SER-287
Other Intervention Name(s)
Eubacterial Spores, Purified Suspension, Encapsulated
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Placebo Pre-Treat
Intervention Type
Drug
Intervention Name(s)
Vancomycin Pre-Treat
Primary Outcome Measure Information:
Title
Safety and Tolerability of SER-287
Description
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.
Time Frame
Day 246
Title
Composition of the Intestinal Microbiome
Description
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.
Time Frame
Baseline and 8 weeks
Title
Engraftment of SER-287 Bacteria in All Treatment Arms
Description
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.
Time Frame
Baseline and 8 weeks
Secondary Outcome Measure Information:
Title
Clinical Remission
Description
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.
Time Frame
8 weeks
Title
Endoscopic Improvement
Description
Defined as a decrease in endoscopic subscore >= 1
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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: Fever > 38.3°C Known or suspected toxic megacolon and/or known small bowel ileus Known history of Crohn's disease Subjects with serum albumin <2.5 g/dL at baseline CMV polymerase chain reaction (PCR) positive from blood plasma at screening Known stool studies positive for ova and/or parasites or stool culture within the 30 days before enrollment 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). Biologic medication (infliximab/ adalimumab/ golimumab/ certolizumab/vedolizumab/ustekinumab/natalizumab) use within 3 months prior to screening Known active malignancy except for basal cell skin cancer, squamous cell skin cancer Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery (excluding cholecystectomy, appendectomy) Subjects with known history of celiac disease or gluten enteropathy Subjects with Clostridium difficile positive stool at Screening Visit Antibiotic use within the prior 1 month before randomization Expected to receive antibiotics within 8 weeks of signing the Informed Consent Form (ICF) (i.e., for planned/anticipated procedure) Received an investigational drug within 1 month before study entry Received an investigational antibody or vaccine within 3 months before study entry Previously enrolled in a SER-109/SER-287 study Received an FMT within the last 6 months 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 Unable to stop steroid enemas or suppositories or mesalamine enemas or suppositories before screening visit Unable to stop opiate treatment unless on a stable dose and no increase in dose planned for the duration of the study Unable to stop probiotics before screening visit Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with medical monitor) Known allergy or intolerance to oral vancomycin -
Facility Information:
Facility Name
Community Clinical Research Network
City
Marlborough
State/Province
Massachusetts
ZIP/Postal Code
01752
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32763240
Citation
Henn MR, O'Brien EJ, Diao L, Feagan BG, Sandborn WJ, Huttenhower C, Wortman JR, McGovern BH, Wang-Weigand S, Lichter DI, Chafee M, Ford CB, Bernardo P, Zhao P, Simmons S, Tomlinson AD, Cook DN, Pomerantz RJ, Misra BK, Aunins JG, Trucksis M. A Phase 1b Safety Study of SER-287, a Spore-Based Microbiome Therapeutic, for Active Mild to Moderate Ulcerative Colitis. Gastroenterology. 2021 Jan;160(1):115-127.e30. doi: 10.1053/j.gastro.2020.07.048. Epub 2020 Aug 4.
Results Reference
derived

Learn more about this trial

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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