E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe ulcerative colitis. |
Colite ulcerosa da moderata a grave. |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis in a moderate or severe form. |
Colite ulcerosa in forma moderata o grave. |
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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 | 100000004856 |
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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 |
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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 |
The primary objective is to assess the efficacy of a top-down approach in achieving histological improvement at week 52, without colectomy and without UC-related hospitalization versus a standard step-up approach. |
L’obiettivo primario è la valutazione dell’efficacia di un approccio top-down nell’ottenere miglioramenti istologici alla settimana 52 senza colectomia e senza ricovero correlato all’UC a confronto con un approccio step-up standard. |
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E.2.2 | Secondary objectives of the trial |
to compare the efficacy of the TD approach to induce histological remission and histological healing in the short-term (week16) vs. the standard SU approach to compare the efficacy of the TD approach to induce clinical remission (combined clinical and endoscopic improvement=sub-score of 0 or 1 with rectal bleeding=0 AND Mayo endoscopic sub score=1) in the short- and long-term (weeks16 and 52) vs the standard SU approach to compare the efficacy of the TD approach to induce short- and long-term mucosal healing (endoscopic and histologic inprovement defined as a defined as a Mayo endoscopic subscore=0 AND a Nancy score=0) vs the standard SU approach (weeks 16 and 52) to compare the safety of the TD approach through week52 vs the standard SU approach to compare the quality of life of patients treated with the TD approach through week 52 vs the standard SU approach to compare the need for colectomies and UC-related hospitalizations in patients treated with the TD approach vs the SU approach |
confrontare efficacia approccio top-down TD nell’indurre remissione istologica e guarigione istologica nel breve termine (sett16) a confronto con approccio step-up SU standard confrontare efficacia appr TD nell’indurre remissione clinica (miglioramento combinato clinico ed endoscopico=subscore di 0 o 1 con sanguinamento rettale=0 E subscore endoscopico Mayo = 1) nel breve e lungo termine (sett16 e 52) a confronto con appr SU standard confrontare efficacia appr TD nell’indurre guarigione mucosale (miglioramento endoscopico e istologico definito come un subscore endoscopico Mayo=0 E un punteggio Nancy=0) nel breve e lungo termine a confronto con appr SU standard (sett16 e sett52) confrontare sicurezza appr TD fino alla sett52 a confronto con appr SU standard confrontare qualità della vita dei pazienti trattati con appr TD fino alla sett52 a confronto con appr SU standard confrontare necessità di colectomie e ricoveri correlati a UC in pazienti trattati con appr TD a confronto con appr SU |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients (age = 18 years and < 75 years) - Established diagnosis of UC (confirmed clinically, endoscopically and histologically) since at least 3 months - Disease duration no longer than 24 months before the screening visit - Ongoing oral 5-ASA treatment =1.6g/day - Having objective signs of moderate-to-severe UC activity, defined by a total Mayo score of 6 to 12 - Proctitis, left-sided or extensive UC - Ability to perform study requirements - Ability to give informed consent according to ICH/ GCP, and national/local |
- Pazienti adulti (età = 18 anni e < 75 anni) - Diagnosi certa di UC (confermata clinicamente, endoscopicamente e istologicamente) da almeno tre mesi - Durata della malattia non superiore ai 24 mesi prima della visita di screening - Trattamento a base di 5-ASA per via orale (= 1.6g/giorno) in corso - Presenza di segni obiettivi di attività da moderata a grave della UC, definita da un punteggio Mayo totale tra 6 e 12 - Proctite, colite ulcerosa sinistra o pancolite - Capacità di svolgere i requisiti dello studio - Capacità di dare il consenso informato in conformità a ICH/GCP e alla normativa nazionale/locale |
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E.4 | Principal exclusion criteria |
- Have received any kind of treatment approved for UC (thiopurine, biologics, tofacitinib) apart from 5-ASA compounds, sulphasalazine or EcN during their UC history - Currently receiving local or systemic steroids (past steroids treatments are accepted) - Have concomitant history of segmental colitis associated to diverticula - Have active infections during the screening phase (patients can be rescreened after the infection is resolved - Have concomitant anti-HBcAb+ and HBsAg- at screening - Have a diagnosis of Crohn's disease - Have any contra-indication to study drugs or procedures - Are pregnant or in active breastfeeding at the time of inclusion. - Have planned intestinal surgery at time of randomization - Any contra-indication to anti-TNF therapy |
- Hanno ricevuto qualunque tipo di trattamento approvato per la UC (tiopurina, farmaci biologici, tofacitinib) salvo composti 5-ASA, salazosulfapiridina o EcN (Escherichia coli Nissle) nel corso della loro UC - Hanno in corso trattamenti con steroidi locali o sistemici (sono accettabili i trattamenti con steroidi già conclusi) - Hanno una concomitante storia di colite segmentale associata a diverticolosi - Hanno infezioni attive nella fase di screening (i pazienti possono ripetere lo screening una volta risolta l’infezione) - Hanno contemporaneamente anti-HBcAb+ e HBsAg- allo screening - Hanno una diagnosi di morbo di Crohn - Hanno controindicazioni ai farmaci o alle procedure dello studio - Sono in gravidanza o in allattamento al momento dell’inclusione - Hanno un intervento chirurgico intestinale programmato all’epoca dell’assegnazione casuale - Hanno controindicazioni alla terapia anti-TNF |
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E.5 End points |
E.5.1 | Primary end point(s) |
Histological improvement (defined as a Nancy index = 1) at week 52, without colectomy and without UC-related hospitalization. |
Miglioramento istologico (definito come indice di Nancy = 1) alla settimana 52, senza colectomia e senza ricovero per CU. |
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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) |
- Histological remission (Nancy Index =0) at week 52 - Histological healing (defined as a Nancy score = 1) at week 16 - Clinical remission (PRO2 remission + endoscopic remission) at week 52 - Clinical remission (PRO2+endoscopic remission) at week 16 - Symptomatic remission (PRO2 remission) at week 16 - Symptomatic remission (PRO2 remission) at week 52 - Endoscopic improvement at week 16 - Endoscopic improvement at week 52 - Endoscopic remission at week 16 - Endoscopic remission at week 52 - Mucosal healing (endoscopic and histologic improvement) at week 16 - Mucosal healing (endoscopic and histologic improvement) at week 52 - Changes in fecal calprotectin levels from baseline - Need for corticosteroids at weeks 16 and 52 - To evaluate and compare the safety of the two strategies in terms of adverse events, serious adverse events, and adverse events leading to discontinuation - Quality of life (measured by the S-IBDQ and SF-36) at weeks 16 and 52 - Rates of colectomies at weeks 16, 52, and 104 (or end of study) - UC-related hospitalizations at weeks 16, 52, and 104 (or end of study) |
- Remissione istologica (Indice di Nancy = 0) a settimana 52 - Guarigione istologica (definita come punteggio di Nancy = 1) a settimana 16 - Remissione clinica (remissione PRO2 + remissione endoscopica) a settimana 52 - Remissione clinica (PRO2 + remissione endoscopica) a settimana 16 - Remissione sintomatica (PRO2 remissione) a settimana 16 - Remissione sintomatica (PRO2 remissione) a settimana 52 - Miglioramento endoscopico a settimana 16 - Miglioramento endoscopico a settimana 52 - Remissione endoscopica a settimana 16 - Remissione endoscopica a settimana 52 - Guarigione della mucosa (miglioramento endoscopico e istologico) a settimana 16 - Guarigione della mucosa (miglioramento endoscopico e istologico) a settimana 52 - Cambiamenti nei livelli di calprotectina fecale rispetto al basale - Necessità di corticosteroidi a settimane 16 e 52 - Valutare e confrontare la sicurezza delle due strategie in termini di eventi avversi, eventi avversi gravi ed eventi avversi che portano alla sospensione - Qualità della vita (misurata da S-IBDQ e SF-36) alle settimane 16 e 52 - Tassi di colectomie alle settimane 16, 52 e 104 (o alla fine dello studio) - Ricoveri per CU alle settimane 16, 52 e 104 (o alla fine dello studio) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 and/or week 52, depending on the endpoints |
Settimana 16 e/o settimana 52, a seconda degli endpoint |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Due diversi approcci terapeutici (step-up e top-down) sono confrontati rispetto allo stesso IMP |
Two different therapeutic approaches (step-up and top-down) are compared with the same IMP |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 75 |
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 |
Austria |
Belgium |
France |
Germany |
Italy |
Portugal |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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 | 3 |
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 | 3 |
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 |