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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: SER-287
* Drug: Placebo
* Drug: Placebo Pre-Treat
* Drug: Vancomycin Pre-Treat


Participation Criteria
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Eligibility Criteria
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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 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weekly SER-287, after Placebo Pre-Treat.<br>Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks | Drug: SER-287<br> <br> * Other names: Eubacterial Spores, Purified Suspension, Encapsulated;Drug: Placebo Pre-Treat<br> <br> |
| Placebo Comparator: Daily placebo, after Placebo Pre-Treat.<br>Placebo pre-treatment, followed by once daily placebo for 8 weeks | Drug: Placebo<br> <br> Drug: Placebo Pre-Treat<br> <br> |
| Experimental: Daily SER-287, after Vanco. Pre-Treat.<br>Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks | Drug: SER-287<br> <br> * Other names: Eubacterial Spores, Purified Suspension, Encapsulated;Drug: Vancomycin Pre-Treat<br> <br> |
| Experimental: Weekly SER-287, after Vanco. Pre-Treat.<br>Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks | Drug: SER-287<br> <br> * Other names: Eubacterial Spores, Purified Suspension, Encapsulated;Drug: Vancomycin Pre-Treat<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 246 | 
| 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. | Baseline and 8 weeks | 
| 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. | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 8 weeks | 
| Endoscopic Improvement | Defined as a decrease in endoscopic subscore >= 1 | 8 weeks |