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 assess the efficacy of visilizumab compared with placebo in retreated subjects.
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E.2.2 | Secondary objectives of the trial |
Secondary: 1) To compare the safety of visilizumab to placebo in retreated subjects. 2) To compare the pharmacokinetics and immunogenicity of visilizumab to placebo in retreated subjects. 3) To compare health-related quality of life (HRQoL) and pharmacoeconomic outcomes of visilizumab to placebo in retreated IVSR-UC subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible subjects will be considered for inclusion in this study if they meet all of the following criteria: 1) Males and females, 18 years of age or older 2) Only 1 prior treatment course with visilizumab (or placebo in a blinded visilizumab study) 3) Response (as defined in parent protocol) of IVSR-UC disease to visilizumab or placebo 4) Symptomatic worsening (ie, an increase of ≥3 points in MTWSI score) from the subject’s best response on the parent study, a score of ≥9, sustained for at least 2 assessments performed at least 1 week apart; and a confirmatory MTWSI of ≥8 within 1 day prior to randomization 5) CD4+ T-cell count ≥ 200 cells/mcL at screening for this protocol, or ≥80% of the subject’s screening baseline count prior to enrollment on the parent study 6) Mayo assessment (including flexible sigmoidoscopy) performed by a trained, blinded evaluating physician within 2 weeks prior to randomization 7) Agreement to use adequate contraception by male or female subjects of reproductive potential throughout the study and for 3 months after receiving the last dose of study drug 8) Negative serum pregnancy test at screening in female subjects of childbearing potential 9) Negative Clostridium difficile test within 10 days prior to the first dose of study drug 10) Ability to understand the purpose and risks of the study and provide signed and dated informed consent. |
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E.4 | Principal exclusion criteria |
Subjects will be ineligible for this study if they meet any one of the following 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) White blood cell (WBC) count less than 2.5 x 10(E3)/mcL; platelet count less than 150 x 10(E3)/mcL; or hemoglobin level less than 8 g/dL. Note: For subjects currently taking a stable dose of 6-MP, AZA, or MTX (for 60 days or more), a WBC count <2.0 x 10(E3)/mcL. Platelet count and hemoglobin level are as stated above. 3) Active medically significant infections, particularly those of viral etiology, eg, known CMV colitis. This includes any incidence of medically significant, opportunistic infections (see Definitions) within the past 12 months 4) Live vaccination within 6 weeks prior to randomization. (Subjects may not receive any vaccine for 60 days after randomization) 5) Significant organ dysfunction, including cardiac, renal, liver, CNS, pulmonary, vascular, gastrointestinal, endocrine, or laboratory abnormality (eg, creatinine ≥1.6 mg/dL; ALT or AST ≥2X the upper limit of normal [ULN]; alkaline phosphatase ≥1.5X ULN); history of myocardial infarction, coronary artery disease, congestive heart failure, or arrhythmias within 6 months prior to consent 6) 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). 7) Seropositive for infection with human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV) 8) Pregnant women or nursing mothers 9) Treatment with any other UC salvage drugs (including but not limited to infliximab or another anti-TNF- α drug, cyclosporine, tacrolimus [FK506], adalimumab, thalidomide, or another experimental agent), or therapies (surgery, pheresis, affinity columns) since the first course of treatment with study drug in the parent visilizumab study 10) Treatment with any other investigational drug or therapy within 60 days prior to randomization 11) Nontherapeutic levels of chronic antiseizure medications in subjects with a history of seizures, as tested within 4 days prior to randomization 12) 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 primary efficacy endpoint is the comparison of the proportion of subjects who respond to retreatment on Day 45 (± 4days) in the visilizumab and placebo groups for the first retreatment course. A subject is defined as a retreatment responder if he/she has a ≥ 3-point (or ≥30%) reduction in the Mayo score from baseline, with the rectal bleeding subscore reduced by at least 1 point, or an actual rectal bleeding subscore of 0 to 1.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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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Please refer to section "Duration of Treatment and Study Period" in the 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 |