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

• 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: Seres Therapeutics, Inc.
• Information provided by (Responsible Party): Seres Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 20, 2015
• First Posted Date: December 1, 2015
• Results First Submitted Date: September 25, 2018
• Results First Posted Date: June 20, 2019
• Last Update Posted Date: June 20, 2019
• Actual Study Start Date: January 13, 2016
• Actual Primary Completion Date: December 6, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2019)

• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: November 25, 2015)

• Safety and tolerability of SER-287 vs. placebo in adult subjects by analysis of AE's, lab values, vital sign, physical exam findings, medical history, and ECG. [ Time Frame: Day 246 ]
• Examination of baseline composition of the intestinal microbiome to the composition [ Time Frame: 8 weeks ]
  Changes in the composition of the microbiome will be characterized by rDNA 16S V4 genomic data sets. Changes will be assessed by total number of unique bacteria and microbial composition
• Engraftment of SER-287 bacteria into the intestinal microbial community in each of the SER-287 arms compared to the placebo arm [ Time Frame: 8 weeks ]
  Microbiome will be characterized by rDNA 16S v4 Genomic Data Sets. Engraftment will be assessed as the outgrowth of bacteria that compromise the SER-287 spore ecology in the subjects GI tract post treatment

Current Secondary Outcome Measures (submitted: March 20, 2019)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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).
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

• Drug: SER-287
  Other Name: Eubacterial Spores, Purified Suspension, Encapsulated
• Drug: Placebo
• Drug: Placebo Pre-Treat
• Drug: Vancomycin Pre-Treat

Study Arms

• Experimental: Weekly SER-287, after Placebo Pre-Treat.
  Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
  Interventions:

  • Drug: SER-287
  • Drug: Placebo Pre-Treat
• Placebo Comparator: Daily placebo, after Placebo Pre-Treat.
  Placebo pre-treatment, followed by once daily placebo for 8 weeks
  Interventions:

  • 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
  Interventions:

  • Drug: SER-287
  • 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
  Interventions:

  • Drug: SER-287
  • Drug: Vancomycin Pre-Treat

• Publications *: 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, Auninš 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 23, 2018): 58
• Original Estimated Enrollment (submitted: November 25, 2015): 55
• Actual Study Completion Date: January 26, 2018
• Actual Primary Completion Date: December 6, 2017 (Final data collection date for primary outcome measure)

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:

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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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02618187
• Other Study ID Numbers: SERES-101
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Seres Therapeutics, Inc.
• Study Sponsor: Seres Therapeutics, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Seres Therapeutics, Inc.
• Verification Date: March 2019