E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis (UC) |
Colite Ulcerativa |
|
E.1.1.1 | Medical condition in easily understood language |
UC is a chronic, inflammatory bowel disease that results in bloody diarrhea |
La colite ulcerativa ¿ una malattia infiammatoria cronica intestinale che provoca una diarrea sanguinolenta |
|
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 | 10066678 |
E.1.2 | Term | Acute ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075635 |
E.1.2 | Term | Acute hemorrhagic 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 | 10033007 |
E.1.2 | Term | Other 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 | 10045366 |
E.1.2 | Term | Ulcerative colitis, unspecified |
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 |
¿ To evaluate the efficacy of UTTR1147A compared with placebo and compared with vedolizumab based on clinical remission |
¿ Valutare l¿efficacia di UTTR1147A rispetto al placebo e rispetto a vedolizumab basato sulla remissione clinica |
|
E.2.2 | Secondary objectives of the trial |
¿ To evaluate the efficacy of UTTR1147A compared with placebo and compared with vedolizumab based on sustained remission, clinical response, endoscopic healing, endoscopic remission, UC bowel movement/abdominal signs and symptoms, and patient-reported health-related quality of life (QOL) ¿ To evaluate the safety of UTTR1147A compared with placebo and compared with vedolizumab ¿ To characterize the pharmacokinetics of UTTR1147A in patients with UC ¿ To evaluate the immune response to UTTR1147A
|
¿ Valutare l¿efficacia di UTTR1147A rispetto al placebo e rispetto a vedolizumab basato sulla remissione sostenuta, risposta clinica, guarigione endoscopica, remissione endoscopica, movimento intestinale CU / segni e sintomi addominali e qualit¿ della vita correlata al paziente (QOL) ¿ Valutare la sicurezza di UTTR1147A rispetto al placebo e rispetto a vedolizumab ¿ Caratterizzare la farmacocinetica di UTTR1147A in pazienti con CU ¿ Valutare la risposta immunitaria a UTTR1147A |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18-80 years
- Diagnosis of UC
- Moderate to severely active UC, defined by the Mayo Clinic Score
- Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment and and/or corticosteroid treatment
- Use of highly effective contraception as defined by the protocol
|
- Età compresa tra 18 - 80 anni - Diagnosi di Colite Ulcerativa (CU) - Conferma di CU da moderata a grave, definita dalla Mayo Clinic Score - Risposta inadeguata, perdita di risposta o intolleranza al precedente trattamento immunosoppressivo e/o trattamento corticosteroideo - Utilizzo di un metodo contraccettivo altamente efficace come definito nel protocollo |
|
E.4 | Principal exclusion criteria |
- History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year and primary sclerosing cholangitis - History of cancer as defined by the protocol - Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or GI disorders (excluding UC) - Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC - Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis and toxic megacolon within 12 months prior to screening - Suspicion of ischemic colitis, radiation colitis, or microscopic colitis - Current fistula or history of fistula, current pericolonic abscess and Stricture (stenosis) of the colon - History or current evidence of unresectable colonic mucosal dysplasia and high-grade colonic mucosal dysplasia - Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents and rituximab - Use of prohibited therapies as defined by the protocol prior to randomization - Evidence or treatment of infections or history of infections as defined by the protocol
|
- Anamnesi di psoriasi o artrite psoriasica; eventuali altre patologie infiammatorie cutanee richiedenti un trattamento con corticosteroidi orali, immunosoppressori o una terapia biologica nell’anno precedente e colangite sclerosante primaria - Anamnesi di tumore come definito nel protocollo - Comorbilità significativa non controllata, quali patologie cardiache, polmonari, renali, epatiche, endocrine o GI (esclusa la CU) - Precedente resezione estesa del colon, colectomia subtotale o totale o proctocolectomia o intervento chirurgico programmato per la CU - Diagnosi di colite indeterminata o colite granulomatosa (di Crohn) e megacolon tossico nei 12 mesi precedenti lo screening - Sospetto di colite ischemica, colite da radiazioni o colite microscopica - Fistola in corso o anamnesi di fistola, ascesso pericolico in corso e restringimento (stenosi) del colon - Precedente trattamento con vedolizumab, etrolizumab, natalizumab, efalizumab o qualsiasi altro agente anti-integrine e rituximab - Uso di terapie "proibite" prima della randomizzazione come definito nel protocollo - Evidenza o trattamento di infezioni o anamnesi di infezioni così come definito nel protocollo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission |
Remissione clinica |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At weeks 10 |
Alla settimana 10 |
|
E.5.2 | Secondary end point(s) |
1. Sustained remission 2. Clinical response 3. Endoscopic healing 4. Endoscopic remission 5. Change from baseline in ulcerative colitis bowel movement signs and symptoms, as assessed by Ulcerative Colitis-Patient-Reported Outcome Signs and Symptoms score (UC PRO/SS) 6. Change from baseline in UC abdominal signs and symptoms, as assessed by UC PRO/SS score 7. Change from baseline in patient-reported health related QOL, as assessed by Inflammatory Bowel Disease Questionnaire score 8. Occurrence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events scale 9. Change in targeted vital signs, physical findings, and clinical laboratory test results during and following study drug administration 10. Serum concentration of UTTR1147A at specified time points 11. Presence of anti-drug antibody (ADA) during the study relative to the presence of ADAs at baseline. |
1. Remissione sostenuta 2. Risposta clinica 3. Guarigione endoscopica 4. Remissione endoscopica 5. Cambiamento dal basale nei segni del movimento intestinale della colite ulcerosa e sintomi, come valutato dal risultato Ulcerativo della Colite-Paziente segnalato Punteggio segni e sintomi (UC PRO / SS) 6. Cambiamento dal basale nei segni e sintomi addominali UC, come valutato dal punteggio UC PRO / SS 7. Cambiamento rispetto al basale nella QOL correlata alla salute riferita dal paziente, come valutato dal punteggio del questionario delle malattie infiammatorie dell'intestino 8. Presenza e gravit¿ degli eventi avversi, con severit¿ determinata secondo i criteri di terminologia comuni del National Cancer Institute per Scala degli eventi avversi 9. Modifica dei segni vitali mirati, risultati fisici e clinici risultati dei test di laboratorio durante e dopo la somministrazione del farmaco in studio 10. Concentrazione sierica di UTTR1147A a determinati intervalli di tempo 11. Presenza di anticorpi anti-farmaco (ADA) durante lo studio relativo al presenza di ADA al basale. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4: At Weeks 10 and 30 5-7: Baseline to Weeks 10 and 30 8-9: Up to 45 months 10: At Weeks 0, 1, 2, 4, 6, 8, 10, 14, 30 and at safety follow-up visit (4 weeks after the last dose of study drug) and at unscheduled visit or disease evaluation or early termination 11: At Weeks 0, 6, 10, 22, 30 and at safety follow-up visit (8 weeks after the last dose of study drug) and at unscheduled visit or disease evaluation or early termination. |
1-4: alle settimane 10 e 30 5-7: baseline alle settimane 10 e 30 8-9: fino a 45 mesi 10: alle settimane 0, 1, 2, 4, 6, 8, 10, 14, 30 e alla visita di controllo di sicurezza (4 settimane dopo l'ultima dose del farmaco in studio) e alla visita non programmata o valutazione della malattia o risoluzione anticipata 11: alle settimane 0, 6, 10, 22, 30 e al follow-up di sicurezza (8 settimane dopo l'ultima dose di farmaco in studio) e in visita o malattia non pianificata valutazione o risoluzione anticipata. |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity; predictive, prognostic, safety, pharmacodynamic biomarkers |
Immugenicit¿; biomarcatori predittivi, prognostici, di sicurezza, farmacodinamici |
|
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 10 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Israel |
Russian Federation |
Serbia |
Ukraine |
United States |
Bulgaria |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
|
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
|
The end of this study is defined as the date when the last patient completes his or her final study visit.
|
La fine di questo studio ¿ definita come la data in cui l'ultimo paziente completa la sua ultima visita di studio. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |