E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis (UC) |
Colite Ulcerosa (CU) |
|
E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis |
Colite Ulcerosa |
|
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 | 100000004856 |
|
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 | 100000004856 |
|
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). |
Valutare l’efficacia e la sicurezza di amiselimod (MT-1303) per via orale rispetto al placebo a 12 settimane come trattamento di induzione in soggetti con colite ulcerosa (CU) attiva da lieve a moderata |
|
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. |
Valutare l’efficacia e la sicurezza del trattamento di mantenimento con amiselimod in aperto per un massimo di 36 settimane (periodo OLE) dopo il completamento del periodo in doppio cieco |
|
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 normal 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) 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. |
Per essere ritenuti idonei, i soggetti dovranno essere uomini o donne di età compresa tra 18 e 75 anni al momento del consenso, con segni vitali nella norma e diagnosi di CU attiva lieve (punteggio Mayo modificato pari a 3 o 4) o moderata (punteggio Mayo modificato pari a 5-8) confermata almeno 12 settimane prima della randomizzazione da evidenze cliniche ed endoscopiche e corroborata da un referto istopatologico. I soggetti dovranno presentare un sottopunteggio endoscopico >= 2 ed evidenze di CU attiva che si estende >= 15 cm dalla rima anale confermate da una colonscopia di screening. I soggetti trattati con 5-aminosalicilati (5-ASA) orali o rettali oppure con corticosteroidi orali (a dosi equivalenti a <= 20 mg di prednisolone) per la CU dovranno essere in terapia con una dose stabile da almeno 28 giorni prima della randomizzazione. I soggetti che completeranno il periodo in doppio cieco dello studio che, secondo il parere dello sperimentatore, trarrebbero beneficio dalla prosecuzione del trattamento potranno partecipare al periodo OLE. |
|
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 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 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, ß-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 Neutrophil count <1.50 × 10^9/L (<1,500/µL). o 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. |
I soggetti verranno esclusi dallo studio in presenza di: • Uno qualsiasi dei seguenti casi: diagnosi di malattia di Crohn, colite indeterminata, colite (pseudomembranosa, microscopica o ischemica) o celiachia, evidenze correnti o recenti (nelle 12 settimane precedenti la randomizzazione) di colite fulminante, proctite (intesa come infiammazione del retto entro 15 cm dalla rima anale), ascesso addominale, megacolon tossico, occlusione o perforazione intestinale, anamnesi positiva per o evidenze di resezione del colon o colectomia subtotale o totale, ileostomia, colostomia, stenosi fissa sintomatica nota dell’intestino, polipi adenomatosi del colon non resecati o displasia della mucosa del colon. • Infezioni clinicamente significative (per es. polmonite, pielonefrite o setticemia) nelle 4 settimane precedenti la randomizzazione o infezioni clinicamente significative necessitanti di ricovero in ospedale nei 6 mesi precedenti la randomizzazione, tubercolosi attiva o latente, infezioni da epatite B, epatite C, virus dell’immunodeficienza umana (HIV) o precedente focolaio di herpes zoster. • Infezione da SARS-CoV-2 attiva o complicanze correlate al COVID-19. • Immunodeficienza primaria o secondaria pregressa o attualmente attiva, presenza di leucoencefalopatia multifocale progressiva (PML) o presenza di malattie demielinizzanti. • Anamnesi positiva per o evidenze di due o più fallimenti con trattamenti biologici per la CU. • Terapia in corso con medicinali per il trattamento della CU diversi da 5-ASA orali o rettali oppure corticosteroidi orali (a dosi equivalenti a <= 20 mg di prednisolone). • Somministrazione di clisteri o supposte (diverse da 5-ASA a dose stabile) per il trattamento della CU nelle 2 settimane precedenti la visita di screening. • Trattamento con probiotici o antidiarroici a dose non stabile nelle 2 settimane precedenti la visita di screening. • Recente infarto del miocardio, angina instabile, ictus, attacco ischemico transitorio, scompenso cardiaco con ricovero in ospedale, insufficienza cardiaca di classe III/IV, blocco atrioventricolare (AV) di secondo o terzo grado di tipo Mobitz II, malattia del nodo del seno, prolungamento dell’intervallo QT, sindrome di Wolff-Parkinson-White o altre anomalie della conduzione, bassa frequenza cardiaca, trattamento in corso con farmaci antiaritmici di classe I o III, calcio-antagonisti che abbassano la frequenza cardiaca, ß bloccanti o altri farmaci che possono ridurre la frequenza cardiaca, alto rischio noto di prolungamento dell’intervallo QT/QTc o anomalie clinicamente significative all’ECG a 12 derivazioni che, secondo lo sperimentatore, potrebbero compromettere la salute del soggetto. • Volume espiratorio massimo nel primo secondo (VEMS) o capacità vitale forzata (CVF) < 70% dei valori previsti allo screening. Per i centri in cui verrà valutata la diffusione alveolo-capillare del monossido di carbonio (DLCO), valore (mL/min/mmHg) < 80% del valore normale previsto per l’età, l’altezza e il sesso. • Edema maculare alla OCT. • Anamnesi positiva per mancata risposta a o fallimento del trattamento con amiselimod o altri modulatori dei recettori della sfingosina 1 fosfato (S1P). • Trapianto di microbiota fecale (FMT) nei 12 mesi precedenti la visita di screening. • Una qualsiasi delle seguenti anomalie di laboratorio: o Emoglobina (Hb) < 9,0 g/dL. o Conta dei globuli bianchi (WBC) < 3,50 × 109/L (< 3.500/µL). o Conta dei neutrofili < 1,50 × 109/L (< 1.500/µL). o Conta dei linfociti < 0,80 × 109/L (< 800/µL). o Aspartato aminotransferasi (AST) o alanina aminotransferarsi (ALT) > 2 volte il limite superiore della norma (ULN). o Bilirubina > 1,5 volte l’ULN; i soggetti con sindrome di Gilbert potranno essere arruolati con livelli di bilirubina totale fino a 5,0 mg/dL. |
|
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. |
Variazione del punteggio Mayo modificato dal basale al Giorno 85. Il punteggio Mayo modificato corrisponde alla somma di: • Sottopunteggio endoscopico (esclusa la friabilità) + • Sottopunteggio relativo al sanguinamento rettale + • Sottopunteggio relativo alla frequenza di evacuazione. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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. |
• Percentuale di soggetti con miglioramento endoscopico al Giorno 85. Per miglioramento endoscopico si intende un sottopunteggio Mayo endoscopico <= 1. • Variazione del punteggio Mayo a 2 componenti (sottopunteggio relativo al sanguinamento rettale + sottopunteggio endoscopico) dal basale al Giorno 85. • Percentuale di soggetti con remissione clinica al Giorno 85 in base al punteggio Mayo modificato, da intendersi come segue: o Sottopunteggio endoscopico <= 1 (esclusa la friabilità) e o Sottopunteggio relativo al sanguinamento rettale pari a 0 e o Riduzione del sottopunteggio relativo alla frequenza di evacuazione pari ad almeno un punto rispetto al basale, in modo da ottenere un sottopunteggio relativo alla frequenza di evacuazione <= 1. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 | Information not present in EudraCT |
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 |
Australia |
Belarus |
Georgia |
Japan |
Korea, Republic of |
Moldova, Republic of |
Russian Federation |
Serbia |
Taiwan |
Ukraine |
United States |
Bulgaria |
Czechia |
Estonia |
Germany |
Hungary |
Italy |
Poland |
Slovakia |
|
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
|
|
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 | 1 |
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 |