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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
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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 | No |
E.3 | Principal inclusion criteria |
1) Males and females, 18 years of age or older. 2) Diagnosis of UC verified by endoscopy performed within 60 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, including massive hemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or perianal abscesses), or toxic megacolon requiring imminent intervention. 2) History of total proctocolectomy, or subtotal colectomy with ileorectal anastomosis. 3) Presence of ileostomy. 4) White blood cell count less than 2.5 x 103/mcL; platelet count less than 150 x 103/mcL; or hemoglobin level less than 8 g/dL. Note the following exceptions for WBC counts only (minimum platelet counts and Hgb levels are the same): - If subject is currently taking a stable dose of 6MP/AZA for 60 days or more, a WBC count less than 2.0 x 103/ mcL. - If subject has initiated treatment with, or increased his/her dose of 6MP, AZA, or methotrexate (MTX) within 60 days prior to consent, a WBC count of less than or equal to 5 x 103/ mcL at the time of sreening. 5) Active medically significant infections, particularly those of viral etiology, e.g, known CMV colitis. This includes any incidence of medically significant opportunistic infections within the past 12 months. 6) Live vaccination within 6 weeks prior to randomization. (Subjects may not receive a live vaccine during dosing or for 60 days after receiving the last dose of study drug.) 7) Significant organ dysfunction, including cardiac, renal, liver, CNS, pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality (eg, creatinine greater than or equal to 1.6 mg/dL; ALT or AST greater than or equal to 2X the upper limit of normal [ULN]; alkaline phosphatase greater than or equal to 1.5X ULN); a history of myocardial infarction, coronary artery disease, congestive heart failure, or arrhythmias within 6 months prior to consent. 8) History or treatment of lymphoproliferative disorder (LPD) or malignancy within the past 5 years (excluding nonmelanoma skin cancer or carcinoma in situ of the cervix). 9) Seropositivity for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV) antibody. 10) Treatment with a first dose of infliximab or another anti-TNF-alpha drug within 4 weeks of randomization, or treatment with a subsequent dose of an anti-TNF-alpha drug within 2 weeks of randomization. 11) Treatment with cyclosporine or tacrolimus (FK506) within 2 weeks prior to randomization. 12) Treatment with any investigational drug or therapy within 60 days prior to randomization, except those mentioned in the above 2 exclusion criteria. 13) Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation. 14) Unable or unwilling to discontinue any UC drug (including but not limited to 6-mercaptopurine, azathioprine, or methotrexate), except glucocorticoids or 5-ASA, immediately prior to randomization. 15) Preganancy or nursing. 16) Nontherapeutic levels of chronic anti-seizure medications in subjects with a prior history of seizures, as tested within 4 days prior to randomization. |
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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 | No |
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.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | 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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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 |