E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the efficacy and safety of oral amiselimod (MT-1303) compared to placebo at 12 weeks as the induction treatment in subjects with active mild to moderate ulcerative colitis (UC). |
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E.2.2 | Secondary objectives of the trial |
Assess the efficacy and safety of maintenance treatment with open-label amiselimod for up to 36 weeks (OLE Period) following completion of the Double-Blind Period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects will be eligible if they are male or female aged between 18 to 75 years at time of consent (inclusive) with stable vital signs and a diagnosis of active mild 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 per day) 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 OLE Period. |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they have: • 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 history of disseminated herpes zoster. • 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 or oral corticosteroids (≤20 mg prednisolone equivalent per day) • 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 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. • History of non-response or treatment failure with amiselimod 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: o Hemoglobin (Hb) <9.0 g/dL. o White blood cell (WBC) count <3.50 × 10^9/L (<3,500/μL). o Absolute neutrophil count <1.50 × 10^9/L (<1,500/μL). o Absolute lymphocyte count <0.80 × 10^9/L (<800/μL). o Aspartate aminotransferase (AST) or alaninevaminotransferase (ALT) >2 × the upper limit of normal (ULN). o 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in the modified Mayo Score at Day 85. The modified Mayo Score is the sum of: • Endoscopy subscore (excludes friability); plus • Rectal bleeding subscore; plus • Stool frequency subscore. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The proportion of subjects with endoscopic improvement at Day 85. Endoscopic improvement is a Mayo endoscopic subscore of ≤1. • The change from Baseline in the 2-component Mayo Score (rectal bleeding plus endoscopic subscores) at Day 85. • The proportion of subjects with clinical remission at Day 85 based on the modified Mayo Score defined as follows: o Endoscopy subscore of ≤1 (excludes friability); and o Rectal bleeding subscore of 0; and o At least one-point decrease in stool frequency subscore from Baseline to achieve a stool frequency subscore of ≤1. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Moldova, Republic of |
Ukraine |
Taiwan |
Australia |
Belarus |
Georgia |
Japan |
Korea, Republic of |
Russian Federation |
Serbia |
United States |
Bulgaria |
Czechia |
Estonia |
Germany |
Hungary |
Italy |
Poland |
Slovakia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |