An Efficacy and Safety Study of LYC-30937-EC in Subjects With Active Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of LYC-30937-EC given orally once daily in subjects with active ulcerative colitis (UC) defined as a total Mayo score (TMS) of 4-11 inclusive, with an endoscopic score of ≥ 2 and a rectal bleeding score of ≥ 1 at screening.

Detailed Description
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Approximately 120 subjects will be randomized to receive either enteric-coated (EC) LYC-30937-EC 25 mg PO once daily (QD) or matching placebo PO QD for the duration of 8 weeks. Randomization will be stratified based on previous exposure to anti-tumor necrosis factor (TNF) agents such that at least 50% of the randomized subjects will be anti-TNF naïve . The study will consist of 3 phases: screening phase: up to 4 weeks double-blind placebo-controlled phase treatment: 8 weeks post-treatment follow-up: 2 weeks Eligible subjects will be randomized at Week 0 (Study Day 1) to either LYC-30937-EC 25 mg or placebo. Screening will occur from Study Days -28 to -1. Randomization and first dosing will occur at Week 0/Study Day 1. Double-blind study visits will occur at Weeks 2, 4, and 8, with the last dose at Week 8/Study Day 57. Subjects will return at Week 10 for a post-treatment safety follow-up visit.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Assess the Efficacy and Safety of Induction Therapy With LYC-30937-EC in Subjects With Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: LYC-30937-EC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical UC diagnosis ≥ 6 months prior to screening with minimum disease extent of ≥ 15cm from anal verge. Active UC defined as a TMS of 4-11 (inclusive) with endoscopic subscore of ≥ 2 and rectal bleeding subscore of ≥ 1 at screening. Females of childbearing potential must have a negative pregnancy test at screening and baseline visits and must agree to use acceptable methods of birth control while in the trial and for 30 days after taking the last dose of study drug. May be currently receiving treatment with oral aminosalicylates (ASA) for ≥ 6 weeks at a stable dose for ≥ 3 weeks prior to the screening screening endoscopy and/or thiopurine at a stable dose ≥ 8 weeks prior to the screening endoscopy and/or prednisone (dose 20 mg daily) or equivalent for ≥ 4 weeks and receiving stable dose for ≥ 2 weeks prior to screening endoscopy able to provide written informed consent and be compliant with study procedures. Exclusion Criteria: History of Crohn's disease (CD) or indeterminate colitis or the presence or history of fistula consistent with CD. Presence of colon polyps. Severe extensive disease that in the investigators discretion is likely to require colonic surgery during the 8 week double-blind portion of the trial (eg, fulminant colitis, toxic megacolon, bowel perforation, evidence of acute abdomen). History of alcohol or drug abuse within 1 year of randomization. History of cancer including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no recurrence for ≥ 1 year prior to screening. History or currently active primary or secondary immunodeficiency. Clinically relevant hepatic, neurologic, pulmonary, ophthalmological, gastrointestinal, endocrine, psychiatric, or other major systemic disease making implementation of the study difficult or that would put the subject at risk by participating in the study Positive test for Clostridium difficile or positive stool culture for enteric pathogens or presence of ova or parasites at screening. Liver function tests > 1.5 x upper limit of normal (ULN) or direct bilirubin > 1.5 x ULN Hemoglobin < 8.5 g/dl Neutrophils < 1500/mm3 White blood cell (WBC) count < 3000/mm3 Platelets < 80000 mm3 International normalized ratio (INR) > 1.5 Treatment with an immunosuppressant agent within 8 weeks of screening. Previous exposure to ≥ 2 approved or investigational biologic agents to treat UC. History of UC treatment with a biologic agent within 12 weeks of screening. Treatment with rectal steroids within 2 weeks of screening. Treatment with an investigational agent within 30 days of screening.

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: LYC-30937-EC 25 mg PO QD<br>LYC-30937-EC 25 mg by mouth once daily for 8 weeks | Drug: LYC-30937-EC<br> <br> |
| Placebo Comparator: Placebo PO QD<br>Matching placebo by mouth once daily for 8 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Achieve Clinical Remission at Week 8 Using Modified Mayo Score. | The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical remission on the modified Mayo score was defined as a Mayo stool frequency subscore of ≤ 1, Mayo rectal bleeding subscore of 0 and a Mayo endoscopy subscore of ≤ 1. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Achieve Clinical Remission at Week 8 Using the Total Mayo Score. | The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical remission on the total Mayo Score is defined as a total Mayo score of ≤ 2, with no individual subscore > 1. | 8 weeks | 
| Number of Subjects With a Clinical Response on the Modified Mayo Score at Week 8. | The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical response on the modified Mayo score at Week 8 was defined as a reduction from the baseline modified Mayo score of ≥ 2 points and ≥ 25%, and a decrease from baseline in rectal bleeding score of ≥ 1 point or absolute rectal bleeding score of ≤ 1 point. | 8 weeks | 
| Number of Subjects With a Clinical Response on the Total Mayo Score at Week 8. | The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical response on the total Mayo score at Week 8 was defined as a reduction from baseline total Mayo score of ≥ 3 points and ≥ 30%, and a decrease from baseline in rectal bleeding score of ≥ 1 point or absolute rectal bleeding score of ≤ 1 point. | 8 weeks | 
| Percent Change From Baseline to Week 8 in Fecal Calprotectin in Subjects With Baseline Fecal Calprotectin ≥ 250 µg/g | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. | Baseline to Week 8 | 
| Percent Change From Baseline in Total Mayo Score at Week 8. | Analyzes the change in total Mayo score score between baseline and Week 8 for all randomized subjects who had total Mayo score scores at both baseline and Week 8. The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. | Baseline to Week 8 |