Clinical trial NCT02618187: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Seres Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-01
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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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Primary outcomes:
measure: Safety and Tolerability of SER-287
timeFrame: Day 246
measure: Composition of the Intestinal Microbiome
timeFrame: Baseline and 8 weeks
measure: Engraftment of SER-287 Bacteria in All Treatment Arms
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Clinical Remission
timeFrame: 8 weeks
measure: Endoscopic Improvement
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Marlborough
country: United States
facility: Community Clinical Research Network
state: Massachusetts
Study officials:
References:
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.