E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis |
Colite ulcerosa |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory bowel disease |
Malattia infiammatoria cronica dell'intestino |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045282 |
E.1.2 | Term | UC |
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 |
Research of predictive factors for response to Tofacitinib therapy in patients with ulcerative rectal colitis. |
Ricerca di fattori predittivi di risposta alla terapia con Tofacitinib in pazienti affetti da retto-colite ulcerosa. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provided written informed consent. 2. >18 years of age 3. Confirmed diagnosis of ulcerative colitis according to international guidelines (ECCO). 4. Patients with moderately-to-severely active disease, as defined as a Mayo score of 6-12, with a rectal bleeding subscore of 1 to 3. 5. Endoscopic Mayo subscore of 2-3. 6. Patients who had failure or intolerant to at least one of the following agents: oral or intravenous glucocorticoids, azathioprine, 6-mercaptopurine, infliximab, golimumab or adalimumab. 7. Because the effects of Tofacitinib on pregnancy are not fully understood, women in childbearing age have to avoid pregnancy. Therefore the above cited patients have to use a suitable contraceptive method such as diaphragm, spiral or contraceptive pill before entering the study, for its entire duration and for 15 weeks after the suspension of the aforementioned drug |
1. Abilità nel comprendere e sottoscrivere il consenso informato 2. Età>18 anni 3. Diagnosi di RCU da almeno 3 mesi, posta in accordo con le correnti line guida nazionali ed internazionali. (ECCO-IGIBD) 4. Pazienti con malattia attiva da moderata a severa, definite da un Mayo score compreso tra 6-12, con un sub-score di sanguinamento rettale tra 1-3 5. Mayo score endoscopica di 2-3 6. Pazienti che hanno precedentemente fallito almeno una delle seguenti terapia convenzionali o biologiche: steroidi orali o endovena, azathioprine o 6-mercaptopurina, farmaci biologici (infliximab, golimumab, adalimumab o vedolizumab) 7. Donne in età fertile che abbiano accettato di non entrare in gravidanza per tutta la durata dello Studio e per le successive 15 settimane dalla sospensione del trattamento in studio, adottando metodi contraccettivi ritenuti idonei quali astinenza, contraccettivi orali, contraccettivi a barriera, spirale. |
|
E.4 | Principal exclusion criteria |
1. Clinical findings suggestive of Crohn’s disease. 2. Ulcerative colitis limited to the distal 15 cm of colon. 3. Clinical signs of fulminant colitis, toxic megacolon, or indeterminate, microscopic, ischemic, or infectious colitis. 4. Patients at high risk of thromboembolism: 1) Patients with heart failure 2) Patients with inherited coagulation disorders 3) Patients who have history of venous thromboembolism, either deep venous thrombosis or pulmonary embolism. 4) Patients who use combined hormonal contraceptives or hormone replacement therapy. 5) Patients with malignancy 6) Patients undergoing major surgery 5. Known hypersensitivity/intolerance to tofacitinib (Xeljanz). 6. Presence of Child-Pugh class C hepatic impairment or eGFR<30 ml/min. 7. Chronic HIV, HBV, HCV infections (excluding patients with HCV infection treated with anti-viral agents in which serum HCV-RNA is not detectable). 8. Active TB or history of latent TB that has not been adequately treated, history of symptomatic herpes zoster (HZV) or any history of disseminated herpes simples (HSV) infections. Active opportunistic, clinically significant infections. 9. History of malignancy in the last 5 years. 10. Pregnant or lactating females. 11. Females of reproductive potential who are unwilling to abide by protocol specified contraceptive methods 8as defined by Appendix 1 in the Study protocol) |
1. Diagnosi di Malattia di Crohn. 2. Rettocolite Ulcerosa distale limitata, con estensione<15 cm dal margine anale. 3. Segni di colite ulcerosa severa acuta, colite fulminante, mega-colon tossico, o diagnosi di colite microscopica, ischemica ed/o infettiva. 4. Pazienti ad elevato rischio di embolia polmonare di cui: 1) Pazienti affetti da insufficienza cardiaca. 2) Pazienti affetti da disturbi ereditari della coagulazione. 3) Pazienti con fenomeni trombo-embolici in atto. 4) Pazienti in terapia ormonale a fini contraccettivi o in terapia ormonale sostitutiva. 5) Pazienti affetti da neoplasie. 6) Pazienti recentemente sottoposti ad interventi chirurgici maggiori. 5. Presenza di ipersensibilità/reazione allergica per tofacitinib (Xeljanz). 6. Presenza di eGFR<30 ml/min o severa disfunzione epatica (Child-Pugh C). 7. Infezioni croniche da HIV, HBV, HCV (fatta eccezione per pazienti con pregressa HCV dopo ciclo di trattamento con agenti antivirali, in cui HCV-RNA non sia più riscontrabile su sangue. 8. Presenza di TB attiva, TB latente non sottoposta a trattamento profilattico, pregressa infezione Herpes Virus, infezioni opportunistiche. 9. Storia di neoplasie nei 5 anni precedenti al baseline. 10. Gravidanza o allattamento. 11. Donne potenzialmente fertili che non voglio o non posso utilizzare metodi contraccettivi altamente efficaci (vedi appendice 1 nel protocollo di studio). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Immunological characterization |
Caratterizzazione immunologica |
|
E.5.1.1 | 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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 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 |