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

Phase 1

Completed

• Conditions: Ulcerative Colitis
• Interventions: Drug: SER-287; Drug: Placebo; Drug: Placebo Pre-Treat; Drug: Vancomycin Pre-Treat

• Registration Number: NCT02618187
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2015-11-20
• Study First Submitted QC: 2015-11-25
• Study First Posted: 2015-12-01
• Study Start: 2016-01-13
• Primary Completion: 2017-12-06
• Study Completion: 2018-01-26
• Results First Submitted: 2018-09-25
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-20
• Last Update Submitted: 2019-03-20
• Results First Posted: 2019-06-20
• Last Update Posted: 2019-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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

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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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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Weekly SER-287, after Placebo Pre-Treat.	SER-287	Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Weekly SER-287, after Placebo Pre-Treat.	Placebo Pre-Treat	Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Daily placebo, after Placebo Pre-Treat.	Placebo	Placebo pre-treatment, followed by once daily placebo for 8 weeks
Daily placebo, after Placebo Pre-Treat.	Placebo Pre-Treat	Placebo pre-treatment, followed by once daily placebo for 8 weeks
Daily SER-287, after Vanco. Pre-Treat.	SER-287	Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks
Daily SER-287, after Vanco. Pre-Treat.	Vancomycin Pre-Treat	Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks
Weekly SER-287, after Vanco. Pre-Treat.	Vancomycin Pre-Treat	Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
Weekly SER-287, after Vanco. Pre-Treat.	SER-287	Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Endoscopic Improvement	8 weeks	Defined as a decrease in endoscopic subscore \>= 1
Clinical Remission	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.

Trial Locations

Locations (1)

Community Clinical Research Network; 🇺🇸 Marlborough, Massachusetts, United States