潰瘍性結腸炎

主要試驗目標是評估口服Amiselimod (MT-1303)相較於安慰劑，用於活躍性輕度至中度潰瘍性大腸炎(UC)受試者，作為誘導性治療，其在第12週時的療效與安全性。次要試驗目標是評估在雙盲治療期完成後，最多36週之Amiselimod開放性維持治療(OLE期)的療效與安全性。

膠囊劑

Amiselimod

130

0.2mg/capsule

第85天修訂後Mayo分數自基礎期以來的變化。修訂後Mayo分數為下列項目的總和：
• 內視鏡子分數(不包括易脆性)；加上
• 直腸出血子分數；加上
• 排便頻率子分數。

1. Male or female subjects aged between 18 to 75 years (inclusive) at the time of the subject’s signing of the
informed consent.
2. Stable vital signs.
• afebrile,
• heart rate 50-100 bpm,
• systolic blood pressure＞90 and ＜160 mmHg,
• diastolic blood pressure ＞50 and ＜100 mmHg,
• respiration rate ＞10 and ＜20/min.
3. Diagnosis of active mild to moderate UC (modified Mayo Score of 3 to 8)confirmed at least 12 weeks prior to
randomization by clinical and endoscopic evidence (corroborated by a histopathology report).
• Mild UC is defined as a modified Mayo Score of 3 or 4.
• Moderate UC is defined as a modified Mayo Score of 5 to 8.
4. An endoscopic subscore from screening colonoscopy of ≥2 as determined by a central reviewer.
5. Evidence of active UC extending ≥15 cm from the anal verge confirmed by a screening colonoscopy.
6. If subjects are receiving oral or rectal 5-aminosalicylates (5-ASAs) or oral corticosteroids (≤20 mg prednisolone
equivalent per day) for treatment of their UC, they must be on a stable dose for at least 28 days prior to
randomization.
7. All women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the Screening Visit and a urine pregnancy test at each subsequent study visit, and additionally at monthly intervals as applicable, and agree to use an acceptable method of contraception throughout their participation in the study and for 12 weeks
after the last dose of IMP.
8. Willingness and ability to complete training in the use of the subject diary and to complete the subject diary in a
timely manner throughout the study.

Exclusion Criteria Related to Ulcerative Colitis
1. Diagnosis of Crohn’s disease, indeterminate colitis, colitis (pseudomembranous, microscopic, or ischemic) or coeliac disease.
2. Current or recent (within 12 weeks prior to randomization) evidence of fulminant colitis, abdominal abscess, toxic
megacolon, bowel obstruction, or bowel perforation.
3. Diagnosis of proctitis, defined as a rectal inflammation within 15 cm from the anal verge.
4. History or evidence of any colonic resection or subtotal colectomy within 1 year prior to randomization.
5. History or evidence of ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
6. History or evidence of unresected adenomatous colonic polyps or colonic mucosal dysplasia.
7. Current need for, or anticipated need for surgical intervention for UC during the study.
Exclusion Criteria Related to General Health and Concomitant Conditions
8. Clinically significant infections (e.g., pneumonia, pyelonephritis, septicemia) within 4 weeks prior to randomization or previous clinically significant infections requiring hospitalization within 6 months prior to randomization
9. Active SARS-CoV-2 infection or complications related to COVID-19.
10. History of lymphoma or other lymphoproliferative disease.
11. Active or latent tuberculosis, as evidenced by any of the following,
a. A positive or indeterminate result for QuantiFERON-TB Gold (or T-SPOT) during the screening period. If an
indeterminate result for QuantiFERON-TB Gold (or T-SPOT) is confirmed, a re-test can be allowed once only.
b. A positive or indeterminate result for chest X-ray that cannot exclude active or latent tuberculosis during the
Screening Period. (Note: If chest X-ray has been done in the past 12 weeks prior to Day 1, no repeat is necessary.
Urine pregnancy test for female subjects to be obtained and results negative prior to chest X-ray.)
12. Infections of hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or varicella zoster virus (VZV) as
evidenced by any of the following,
a. Positive results for active HBV infection (positive HBV surface Ag; positive HBV core Ab with negative HBV surface Ab), HCV (HCV RNA), or HIV tests during the screening period.
b. History of disseminated herpes zoster.
13. History of or currently active primary or secondary immunodeficiency.
14. History of progressive multifocal leukoencephalopathy (PML) or presence of PML as determined by a positive
subjective symptom with a confirmed objective evaluation prior to randomization based on the PML checklist.
15. History or presence of demyelinating diseases.
16. Active C. difficile infection. 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.
17. Receipt of a live or live-attenuated vaccine (including VZV vaccine) within 4 weeks prior to randomization. (Note:
non-live vaccinations are permitted.)
18. Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic
attack, decompensated heart failure with hospitalization, or Class III/IV heart failure.
19. History of Mobitz Type II 2nd degree or 3rd degree atrioventricular (AV) block or
sick sinus syndrome.
20. Ongoing treatment with Class I or Class III anti-arrhythmic drugs, or with heartrate- lowering calcium-channel
blockers (e.g., verapamil or diltiazem), β-blockers, or with any other drugs which can reduce the heart rate (e.g., ivabradine, magnesium sulfate).
21. Known high risk for QT/QTc prolongation (e.g., family history of long QT syndrome or sudden death).
22. History or presence (within 5 years prior to screening) of malignancy, except for successfully treated basal cell and in situ squamous cell carcinomas of the skin.
23. History or presence of macular oedema (as assessed by OCT during screening), uveitis, or evolutive retinopathy, or any other condition that could increase the risk of macular oedema in the opinion of the Investigator.
24. Diabetes mellitus type 1 OR diabetes mellitus type 2 with use of insulin or with ＞8 years disease duration after its diagnosis or with significant comorbid conditions (e.g., retinopathy, nephropathy, or neuropathy). Subjects with hemoglobin A1c (HbA1c) ＞7.5% during the screening period will also be excluded.
25. History or evidence of substance abuse (e.g., drug or alcohol), or any other factor (e.g., serious psychiatric
condition) that limits the subject’s ability to cooperate with the study procedures.
Exclusion Criteria Related to Administered Medications
26. History or evidence of two or more failures with biologic treatment for UC (primary non-responders).
27. Unstable dose of oral or rectal 5-ASAs or oral corticosteroids within 28 days prior to randomization.
28. Use of any of the following within 28 days prior to the Screening Visit or as designated:
a. IV corticosteroid within 4 weeks of the Screening Visit; rectal corticosteroid within 2 weeks of the Screening Visit.
b. Cyclosporine, mycophenolate mofetil, or thalidomide.
c. Tacrolimus.
d. Intravenous immunoglobulin, plasmapheresis, or cytapheresis therapy.
e. Any biologics or newly approved UC treatment agents (e.g., infliximab, adalimumab, certolizumab, golimumab,
etanercept, vedolizumab, ustekinumab, tofacitinib, or natalizumab) within 8 weeks of the Screening Visit.
29. Use of immunosuppressants (e.g., AZA, 6-MP, or MTX) 28 days prior to randomization.
30. Unstable dose of probiotics within 14 days prior to the Screening Visit.
31. Unstable dose of antidiarrheals (loperamide, diphenoxylate) within 14 days prior to the Screening Visit.
32. Use of enemas or suppositories (other than stable dose of 5-ASAs) for treatment of UC within 14 days prior to the Screening Visit.
33. Use of fecal microbiota transplantation (FMT) within 12 months prior to the Screening Visit.
34. History or evidence of use of lymphocyte-depleting therapies (e.g., anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab).
35. For WOCBP, initiation of oral contraceptives, or having an unstable dose of oral contraceptives, within 12 weeks prior to the Screening Visit.
36. History of non-response or treatment failure with sphingosine 1-phosphate (S1P) receptor modulators including
amiselimod, fingolimod, ozanimod, and etrasimod.
37. Known history of allergy, hypersensitivity or any serious reaction to any component of the IMP (e.g., mannitol or
gelatin).
38. Previous treatment with any investigational agent within 12 weeks prior to randomization OR 5 half-lives of the investigational product, whichever is longer.
39. Plan to participate or are currently participating in any other interventional clinical trial (in which an investigational treatment or approved therapy for investigational use is administered) during this study.
Exclusion Criteria Related to ECG and PFT Findings
40. Low heart rate (＜50 beats per minute [bpm]), in 12-lead ECG at screening or randomization (pre-dose).
41. Corrected QT interval using Fridericia’s formula (QTcF) ＞=470 milliseconds (msecs) for females and ≥ 450 msec for males in 12-lead ECG at screening or randomization (pre-dose).
42. Any conduction abnormalities, e.g., Wolff Parkinson White.
43. Clinically significant abnormal findings in 12-lead ECG (at screening or randomization [pre-dose]) and/or in 24-hour ECG (at screening) that the Investigator considers may jeopardize the subject’s health (e.g., acute ischemia,
conduction abnormalities, or arrhythmias).
44. Forced expiratory volume in one second (FEV1) or forced expiratory vital capacity (FVC) ＜70% of predicted values at screening.
45. For sites where DLCO will be assessed, the value (mL/min/mmHg) is ＜80% of the predicted normal value for age, height, and gender.
Exclusion Criteria Related to Laboratory Findings
46. Any of the following laboratory abnormalities during the screening period:
a. Hemoglobin (Hb) ＜9.0 g/dL.
b. White blood cell (WBC) count ＜3.50 x＜ 109/L ＜3,500/μL).
c. Absolute neutrophil count ＜1.50 x ＜109/L (＜1,500/μL).
d. Absolute lymphocyte count＜0.80 x ＜ 109/L (＜800/μL).
e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN).
f. Bilirubin >1.5 x the ULN. Subjects with Gilbert’s syndrome may be enrolled with total bilirubin up to 5.0 mg/dl.
47. Positive stool tests for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile (C. difficile) at the Screening Visit.
48. (For female subjects only) A positive pregnancy test at Screening Visit (serum betahuman chorionic gonadotropin [hCG] level or urine dipstick) or Baseline Visit (urine dipstick) except for provided proof of menopause (hormonal or
surgical). Subjects who are breastfeeding are also excluded.
General Exclusion
49. Any physical or mental conditions which would interfere with the study participation, collection of data, or study
completion.
50. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for
enrollment.