E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Diagnosis of UC according to Lennard-Jones criteria - Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally. - Severe acute flare of UC with a Lichtiger Index score > 10. - Refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of methylprednisolone or equivalent) given for at least 5 days.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045282 |
E.1.2 | Term | UC |
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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 |
This randomized, open-label, multicenter trial aims to demonstrate that treatment failure is less frequent in cyclosporine than in infliximab on short-term response in steroid-refractory severe attacks of ulcerative colitis patients. END POINT PRIMARY END POINT Percentage of patients with treatment failure defined as: absence of clinical response at D7 (Lichtiger Index score<10 with a decrease of at least 3 points compared with the baseline score – see appendix), or absence of remission without steroids at D98 (remission is defined as a Mayo Disease Activity Index (DAI) score2 without any subscore>1), or relapse between D7 and D98 (relapse is proven as a success at D7 and a reascenscion of at least 3 points of the Lichtiger Index score compared with the previous last value for at least 3 consecutive days leading to a new treatment) or severe adverse event leading to treatment interruption between D0 and D9 or colectomy between D0 and D98. or fatality between D0 and D98
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E.2.2 | Secondary objectives of the trial |
- SECONDARY END POINTS •Percentage of patients in clinical response at D7, D14, D28, D42 and D98 defined as Lichtiger Index score<10 with a decrease of at least 3 points compared with the baseline score. Percentage of patients in remission at D7, D42 and D98 Lichtiger Index score at D7, D14, D28, D42, D98 Mayo Disease Activity Index score at D7, D14, D42 and D98 Time to discharge Endoscopic response (using the subscore of the Mayo DAI) at D7, D42 and D98. Colectomy rate at D98. Steroid dosage at D7, D14, D28, D42, and D98 Number of adverse events (see below) CMV infection will be assessed at D7 and D98
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age > 18 years. - Diagnosis of UC according to Lennard-Jones criteria (Appendix 1). - Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally. - Severe acute flare of UC with a Lichtiger Index score > 10 (Appendix 2). - Refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of methylprednisolone or equivalent) given for at least 5 days. - Adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination.
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E.4 | Principal exclusion criteria |
- Pregnant or breast-feeding woman. - Previous treatment with cyclosporine or infliximab. - Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before inclusion. - Indication for immediate surgery. - History of colorectal dysplasia. - Diagnosis of Crohn's disease. - Positive stool tests for amoebiasis and/or positive bacteriological culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools. - Renal failure (creatininemia > upper limit of normal laboratory value). - Uncontrolled high blood pressure. - HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months. - Uncontrolled bacterial or active viral infection. - Past medical history of malignant condition in the last 5 years (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers. - Past medical history of myocardial infarction or heart failure. - Intradermal reaction to Tuberculin (Tubertest® 5 units) > 5mm. - Active tuberculosis - Untreated latent tuberculosis (see national recommendations. Appendix 3). - Abnormal blood count with polynuclear neutrophils < 1,500 G/L or white cells < 3,000, or platelets < 100,000 G/L. - Unexplained rise higher than 3 times the normal level for transaminases, alkaline phosphatases and/or higher than twice the normal level for bilirubin. - Non-compliant subjects. - Participation in another therapeutic study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with treatment failure defined as: absence of clinical response at D7 (Lichtiger Index score<10 with a decrease of at least 3 points compared with the baseline score – see appendix), or absence of remission without steroids at D98 (remission is defined as a Mayo Disease Activity Index (DAI) score2 without any subscore>1), or relapse between D7 and D98 (relapse is proven as a success at D7 and a reascenscion of at least 3 points of the Lichtiger Index score compared with the previous last value for at least 3 consecutive days leading to a new treatment) or severe adverse event leading to treatment interruption between D0 and D98 or colectomy between D0 and D98. or fatality between D0 and D98
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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
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INCLUSION PERIOD: 24 months.
STUDY DURATION: 27 months.
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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 | |
E.8.9.1 | In the Member State concerned months | 51 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 51 |