E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis |
Colite Ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis |
Colite Ulcerosa |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
¿ To assess the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects with moderately to severely active UC who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. |
¿ Valutare l¿effetto del trattamento di mantenimento con vedolizumab SC sulla remissione clinica alla Settimana 52 in soggetti con CU da moderatamente a gravemente attiva che hanno ottenuto una risposta clinica alla Settimana 6 a seguito della somministrazione di vedolizumab EV alle Settimane 0 e 2. |
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E.2.2 | Secondary objectives of the trial |
¿ To determine the effect of vedolizumab SC maintenance treatment on mucosal healing at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
¿ To determine the effect of vedolizumab SC maintenance treatment on durable clinical response at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
¿ To determine the effect of vedolizumab SC maintenance treatment on durable clinical remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
¿ To determine the effect of vedolizumab SC maintenance treatment on corticosteroid free remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
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¿ Determinare l¿effetto del trattamento di mantenimento con vedolizumab SC sulla guarigione mucosale alla Sett. 52 in soggetti che hanno ottenuto una risposta clinica alla Sett. 6 a seguito della sommin. di vedolizumab EV alle Sett. 0 e 2. ¿ Determinare l¿effetto del trattamento di mantenimento con vedolizumab SC sulla risposta clinica duratura alla Sett. 52 in soggetti che hanno ottenuto una risposta clinica alla Sett. 6 a seguito della sommin. di vedolizumab EV alle Sett. 0 e 2. ¿ Determinare l¿effetto del trattamento di mantenimento con vedolizumab SC sulla remissione clinica duratura alla Sett. 52 in soggetti che hanno ottenuto una risposta clinica alla Sett. 6 a seguito della sommin. di vedolizumab EV alle Sett. 0 e 2. ¿ Determinare l¿effetto del trattamento di mantenimento con vedolizumab SC sulla remissione senza corticosteroidi alla Sett. 52 in soggetti che hanno ottenuto una risposta clinica alla Sett. 6 a seguito della sommin. di vedolizumab EV alle Sett. 0 e 2.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has a diagnosis of UC established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.
2. The subject has moderately to severely active UC as determined by a complete Mayo score of 6-12 with an endoscopic subscore =2 within 10 days prior to the first dose of study drug.
3. The subject has evidence of UC extending proximal to the rectum (=15 cm of involved colon).
4. The subject has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: immunomodulators, corticosteroids, or TNF-alpha.
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Il soggetto presenta una diagnosi di CU stabilita almeno 6 mesi prima dello screening tramite evidenza clinica ed endoscopica e corroborata da un referto istopatologico. Il soggetto presenta CU da moderatamente a gravemente attiva in base a un punteggio Mayo totale di 6-12, con un sottopunteggio endoscopico =2 entro 10 giorni precedenti la prima dose del farmaco dello studio. Il soggetto mostra evidenza di CU che si estende in prossimità del retto (=15 cm di colon interessati). Il soggetto ha dimostrato una risposta inadeguata, una perdita della risposta o intolleranza ad almeno 1 dei seguenti agenti: immunomodulatori, corticosteroidi o TNF-a.
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E.4 | Principal exclusion criteria |
1. The subject has clinical evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
2. The subject has had extensive colonic resection, subtotal or total colectomy.
3. The subject has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
4. The subject has received any of the investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib, except for those specifically listed in the protocol) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).
5. The subject has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (which ever is longer).
6. The subject currently requires or is anticipated to require surgical intervention for UC during the study.
7. The subject has a history or evidence of adenomatous colonic polyps that have not been removed, or has a history or evidence of colonic mucosal dysplasia.
8. The subject has a suspected or confirmed diagnosis of Crohn’s entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
9. The subject has evidence of an active infection during the Screening Period.
10. The subject has evidence of, or treatment for, C. difficile infection or other intestinal pathogen with 28 days prior to first dose of study drug.
11. The subject has chronic HBV or HCV infection.
12. The subject has active or latent TB, regardless of treatment history.
13. The subject has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
14. The subject has received any live vaccinations within 30 days prior to screening.
15. The subject had a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection.
16. The subject has used a topical (rectal) treatment with 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug. |
Il soggetto è stato sottoposto a resezione estesa del colon, colectomia subtotale o totale. Il soggetto mostra qualsiasi evidenza di infezione attiva durante lo screening. Il soggetto ha un elenco di controllo soggettivo per la leucoencefalopatia multifocale progressiva (LMP) positivo prima della somministrazione del farmaco dello studio. Il soggetto ha ricevuto qualsiasi agente biologico o biosimilare sperimentale o approvato entro 60 giorni o 5 emivite precedenti lo screening, a seconda di quale sia il periodo più lungo. Il soggetto è stato esposto precedentemente a vedolizumab. Il soggetto è stato esposto precedentemente a natalizumab, efalizumab o rituximab.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects with clinical remission, defined as a complete Mayo score of =2 points and no individual subscore >1 point, at Week 52. |
• Percentuale di soggetti con remissione clinica, definita come punteggio Mayo totale =2 punti e nessun sottopunteggio individuale >1 punto, alla Settimana 52. |
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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) |
¿ Proportion of subjects with mucosal healing, defined as Mayo endoscopic subscore of =1 point, at Week 52. ¿ Proportion of subjects with durable clinical response, defined as clinical response at Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of =3 points and =30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of =1 point or absolute rectal bleeding subscore of =1 point. ¿ Proportion of subjects with durable clinical remission, defined as clinical remission at Weeks 6 and 52. ¿ Proportion of subjects with corticosteroid-free remission, defined as subjects using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. |
¿ Percentuale di soggetti con guarigione mucosale, definita come sottopunteggio Mayo endoscopico =1 punto, alla Settimana 52. ¿ Percentuale di soggetti con risposta clinica duratura, definita come risposta clinica alle Settimane 6 e 52, ove la risposta clinica ¿ definita come riduzione del punteggio Mayo totale =3 punti e =30% rispetto al basale (Settimana 0) con concomitante riduzione del sottopunteggio di sanguinamento rettale =1 punto o sottopunteggio assoluto di sanguinamento rettale =1 punto. ¿ Percentuale di soggetti con remissione clinica duratura, definita come remissione clinica alle Settimane 6 e 52. ¿ Percentuale di soggetti con remissione senza corticosteroidi, definita come soggetti che utilizzavano corticosteroidi orali al basale (Settimana 0) che hanno interrotto i corticosteroidi orali e sono in remissione clinica alla Settimana 52.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52: Mucosal healing and corticosteroid-free remission. Week 6 and Week 52: Durable clinical response and durable clinical remission. |
Settimana 52: guarigione mucosale e remissione senza corticosteroidi. Settimana 6 e Settimana 52: risposta clinica duratura e remissione clinica duratura.
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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 | 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 | 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) | Yes |
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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
Turkey |
Ukraine |
United States |
Belgium |
Bulgaria |
Croatia |
Denmark |
Estonia |
France |
Germany |
Hungary |
Italy |
Lithuania |
Netherlands |
Poland |
Romania |
Slovakia |
Spain |
Sweden |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of trial will be the date of the last visit of the last subject at the Week 68 Follow-up visit |
Il termine dello Studio sar¿ il giorno dell'ultima visita dell'ultimo soggetti alla visita di follow-up della settimana 68. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |