E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intravenous steroid-refractory ulcerative colitis (IVSR-UC) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: To compare the efficacy of visilizumab at 5 mcg/kg/day administered intravenously (IV) on Days 1 and 2 to placebo in subjects with IVSR-UC. |
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E.2.2 | Secondary objectives of the trial |
Secondary: To compare the safety, immunogenicity, health-related quality of life, and pharmacoeconomic outcomes of visilizumab to placebo in IV steroid-refractory UC subjects. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Males and females, 18 years of age or older. 2) Diagnosis of UC verified by colonoscopy or barium enema performed within 36 months prior to consent. 3) Severe active disease, as defined by a Modified Truelove & Witts’ Severity Index (MTWSI; also known as Lichtiger Score) greater than or equal to 11 at consent, with a confirmatory MTWSI greater than or equal to 10 on or after the fifth consecutive day of IV steroids and within 1 day prior to randomization. 4) Mayo score greater than or equal to 10 and a Mayo mucosal subscore greater than or equal to 2 after a minimum of 3 consecutive days (ie, on or after the fourth consecutive day) of IV steroids. 5) Adequate contraception from the day of consent through 3 months after the last dose of study drug. 6) Negative serum pregnancy test at screening. 7) Negative Clostridium difficile test within 10 days prior to the first dose of study drug. 8) Signed and dated informed consent and HIPAA if applicable. |
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E.4 | Principal exclusion criteria |
1) UC requiring immediate surgical, endoscopic, or radiologic interventions. 2) History of prior colorectal surgery or ileostomy. 3) White blood cell count less than 2.5 x 10 to the power 3/mcL; platelet count less than 150 x 10 to the power 3/mcL; or hemoglobin level less than 8 g/dL. 4) Active medically significant infections, including prior opportunistic infections within the past 12 months. 5) Live vaccination within 6 weeks prior to randomization. 6) History of deep vein thrombosis or pulmonary embolus. 7) Significant organ dysfunction, including cardiac, renal, liver, CNS, pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality. 8) History of lymphoproliferative disorder (LPD) or malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix that has been adequately treated. 9) Seropositivity for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV). 10) Pregnancy or nursing. 11) Infliximab treatment within 4 weeks of first dose or 2 weeks of subsequent dose. 12) Treatment with cyclosporine or tacrolimus (FK506) within 2 weeks prior to randomization. 13) Treatment with any other investigational drugs or therapies within 60 days prior to randomization. 14) Initiation or increase of dosing of 6-mercaptopurine, azathioprine, or methotrexate within 60 days immediately prior to randomization. 15) Failure to discontinue any UC drug (including but not limited to 6-mercaptopurine, azathioprine, or methotrexate), except glucocorticoids or 5-ASA, prior to randomization. 16) Nontherapeutic levels of chronic anti-seizure medications in subjects with a prior history of seizures. 17) Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The comparison of the proportion of subjects who respond to treatment on Day 45 (± 4 days) in the visilizumab and placebo groups. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Quality of Life |
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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) | 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) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Refer to 'Duration of Treatment and Study Period' in protocol study synopsis. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |