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

Seres Therapeutics

Status and phase: Completed; Phase 1

Conditions: Ulcerative Colitis

Treatments: Drug: SER-287; Drug: Vancomycin Pre-Treat; Drug: Placebo; Drug: Placebo Pre-Treat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02618187

SERES-101

Details and patient eligibility

About

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

Full 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).

Enrollment: 58 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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58 participants in 4 patient groups, including a placebo group

Weekly SER-287, after Placebo Pre-Treat.

Experimental group

Description:

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

Treatment:

Drug: SER-287

Drug: Placebo Pre-Treat

Daily placebo, after Placebo Pre-Treat.

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo Pre-Treat

Drug: Placebo

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

Experimental group

Description:

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

Treatment:

Drug: SER-287

Drug: Vancomycin Pre-Treat

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

Experimental group

Description:

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

Treatment:

Drug: SER-287

Drug: Vancomycin Pre-Treat