Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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The study will assess the efficacy and safety of oral MT-1303 compared to placebo at 12 weeks as the induction treatment in subjects with active mild to moderate ulcerative colitis (UC), as well as maintenance treatment with open-label MT-1303 for up to 36 weeks.

Detailed Description
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This is a Phase 2, randomized, double-blinded, placebo-controlled 3-arm, multi-center, parallel-group study with an open-label extension (OLE) period. The study includes a Screening Period (of up to 28 days) and a 12-week Double-Blind Period (Day 1 through Day 85) for all subjects. Subjects completing the Double-Blind Period through Day 85 will be provided the opportunity to continue in the OLE Period of the study to receive treatment through approximately one year. Subjects who do not participate in the OLE Period will be followed for 84 days in a Safety Follow-up Period.

Official Title
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A Phase 2, Randomized, Double-Blinded, Placebo Controlled, Parallel Group Study Evaluating the Efficacy and Safety of Amiselimod (MT-1303) in Subjects With Mild to Moderate Ulcerative Colitis (UC)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Low Dose MT-1303
* Drug: High Dose MT-1303
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible if they are male or female aged between 18 to 75 years at time of consent (inclusive) with normal vital signs and a diagnosis of active mild ulcerative colitis (UC) (modified Mayo Score of 3 or 4) or moderate UC (modified Mayo Score of 5 to 8) confirmed at least 12 weeks prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. Subjects must have an endoscopic subscore of ≥2 from and evidence of active UC extending ≥15 cm from the anal verge confirmed by a screening colonoscopy. If subjects are receiving oral or rectal 5-aminosalicylates (5-ASAs) or oral corticosteroids (≤20 mg prednisolone equivalent) for treatment of their UC, they must be on a stable dose for at least 28 days prior to randomization. Subjects who complete the Double-Blind Period of the study who, in the opinion of the Investigator, would benefit from continued treatment, may participate in the Open Label Extension (OLE) Period. Exclusion Criteria: Any of the following: a diagnosis of Crohn's disease, indeterminate colitis, colitis (pseudomembranous, microscopic, or ischemic) or coeliac disease, current or recent (within 12 weeks prior to randomization) evidence of fulminant colitis, proctitis (defined as a rectal inflammation within 15 cm from the anal verge), abdominal abscess, toxic megacolon, bowel obstruction, or bowel perforation; a history or evidence of any colonic resection or subtotal or total colectomy, ileostomy, colostomy, known fixed symptomatic stenosis of the intestine, unresected adenomatous colonic polyps, or colonic mucosal dysplasia. Clinically significant infections (e.g., pneumonia, pyelonephritis, or septicemia) within 4 weeks prior to randomization or previous clinically significant infections requiring hospitalization within 6 months prior to randomization, active or latent tuberculosis, infections of hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or previous shingles outbreak. Active SARS-CoV-2 infection or complications related to COVID-19. A history of, or currently active, primary or secondary immunodeficiency, presence of progressive multifocal leukoencephalopathy (PML), or presence of demyelinating diseases. A history or evidence of two or more failures with biologic treatment for UC. Currently taking any medication for treatment of UC other than oral or rectal 5-ASAs (5-aminosalicylic acids) or oral corticosteroids (≤20 mg prednisolone equivalent) Been taking enemas or suppositories (other than stable dose of 5-ASA) for treatment of UC within 2 weeks prior to the Screening Visit. Been taking an unstable dose of probiotics or antidiarrheals 2 weeks prior to the Screening Visit. Had recent myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, Class III/IV heart failure, Mobitz Type II 2nd degree or 3rd degree atrioventricular (AV) block, sick sinus syndrome, prolonged QT interval, Wolff Parkinson White or other conduction abnormalities, low heart rate, ongoing treatment with Class I or Class III anti-arrhythmic drugs, heart-rate-lowering calcium-channel blockers, β blockers or with any other drugs which can reduce the heart rate, have known high risk for QT/QTc prolongation, or have clinically significant abnormal findings in 12-lead ECG that the Investigator considers may jeopardize the subject's health. Forced expiratory volume in one second (FEV1) or forced expiratory vital capacity (FVC) <70% of predicted values at screening. For sites where DLCO (diffusing capacity of the lungs for carbon monoxide) will be assessed, the value (mL/min/mmHg) is < 80% of the predicted normal value for age, height, and gender. Macular oedema as assessed by OCT (Optical Coherence Tomography). History of non-response or treatment failure with MT-1303 or other sphingosine 1 phosphate (S1P) receptor modulators. Fecal microbiota transplantation (FMT) within 12 months prior to the Screening Visit. Any of the following laboratory abnormalities: Hemoglobin (Hb) <9.0 g/dL. White blood cell (WBC) count <3.50 × 109/L (<3,500/µL). Neutrophil count <1.50 × 109/L (<1,500/µL). Lymphocyte count <0.80 × 109/L (<800/µL). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN). Bilirubin >1.5 x the ULN; subjects with Gilbert's syndrome may be enrolled with total bilirubin up to 5.0 mg/dl. Positive stool tests for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile (C. difficile) during the Screening Period. If subject has a history of recent C. difficile infection (within 60 days prior to Screening Visit), they should not be considered for study enrollment until subject has been treated for C. difficile and is symptom free for at least 14 days prior to the Screening Visit. Any physical or mental conditions which would interfere with the study participation, collection of data, or study completion as determined by the Investigator.

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: Low Dose<br>MT-1303 loading dose of 0.4 mg once daily (QD) (Day 1-14) then maintenance dose of 0.2 mg QD (Day 15-85) | Drug: Low Dose MT-1303<br>* MT-1303 loading dose of 0.4 mg once daily (QD) (Day 1-14) then maintenance dose of 0.2 mg QD (Day 15-85)<br>|
| Experimental: High Dose<br>MT-1303 loading dose of 0.8 mg QD (Day 1-14) then maintenance dose of 0.4 mg QD (Day 15-85) | Drug: High Dose MT-1303<br>* MT-1303 loading dose of 0.8 mg QD (Day 1-14) then maintenance dose of 0.4 mg QD (Day 15-85)<br>|
| Placebo Comparator: Placebo<br>Matching placebo, QD (Day 1-85) | Drug: Placebo<br>* Matching placebo, QD (Day 1-85)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the modified Mayo Score at Day 85 | The modified Mayo Score for ulcerative colitis disease activity provides an assessment of disease severity and can be used to monitor subjects during therapy. Scoring is accomplished by summation of subscores for endoscopic findings, stool frequency, and rectal bleeding, with higher scores indicating worse severity. Each subscore ranges from 0 to 3. The modified Mayo Score is defined as the sum of the endoscopy findings subscore + stool frequency subscore + rectal bleeding subscore, with a range from 0 to 9. | Baseline to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with endoscopic improvement at Day 85 | The Mayo endoscopic subscore ranges from 0 to 3, with higher scores indicating worse severity. Endoscopic improvement is a Mayo endoscopic subscore of ≤1. | Baseline to Day 85 | 
| The change from Baseline in the 2-component Mayo Score at Day 85. | 2-component Mayo scoring is accomplished by summation of subscores for endoscopic findings and rectal bleeding, with higher scores indicating worse severity. Each subscore ranges from 0 to 3. The 2-component Mayo Score is the sum of the rectal bleeding plus endoscopic subscores, with a range from 0 to 6. | Baseline to Day 85 | 
| The proportion of subjects with clinical remission at Day 85 based on the modified Mayo Score | The modified Mayo Score for ulcerative colitis disease activity provides an assessment of disease severity and can be used to monitor subjects during therapy. Scoring is accomplished by summation of subscores for endoscopic findings, stool frequency, and rectal bleeding, with higher scores indicating worse severity. Each subscore ranges from 0 to 3. Remission is defined as follows: Endoscopy subscore of ≤1 (excludes friability); and Rectal bleeding subscore of 0; and At least one-point decrease in stool frequency subscore from Baseline to achieve a stool frequency subscore of ≤1. | Baseline to Day 85 |