| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Crohn’s disease (CD) in patients with at least one perianal fistula. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10011401 | |
| 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 | | To evaluate the clinical activity of two consecutive daily doses of 10 mcg/kg visilizumab administered intravenously to patients with draining perianal fistulas associated with Crohn’s disease | |
| E.2.2 | Secondary objectives of the trial | 1) To evaluate the pharmacokinetics of two consecutive daily doses of 10 mcg/kg visilizumab administered intravenously in this patient population
2) To determine the risk-benefit relationship of visilizumab in this patient population
3) To assess immunogenicity of visilizumab in this patient population
4) To evaluate the safety, tolerability, clinical activity, pharmacokinetics, and immunogenicity of retreatment (if warranted) of two consecutive daily doses of 10 mcg/kg visilizumab in patients with perianal fistulas associated with Crohn’s disease | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Eligible patients will be considered for inclusion in this study if they meet all of the following criteria:
1) Male or female, 18 to 70 years of age
2) A diagnosis of CD and at least one documented external, draining, perianal fistula
3) Patients with reproductive potential who agree to use double-barrier methods of contraception during the study and for 3 months after receiving study drug
4) Women of childbearing potential who have a negative serum pregnancy test at baseline screening
5) Who have tested negative for Clostridium difficile within 3 weeks prior to treatment with study drug
6) Who are capable of understanding the purpose and risks of the study and who provide signed and dated informed consent and an authorization to use protected health information (US sites only)
7) Who have EBV DNA titers up to 30,000 copies/mL | |
| E.4 | Principal exclusion criteria | Patients will be ineligible for this study if they meet any one of the following criteria:
1) History of lymphoproliferative disorder or a prior malignancy within 5 years or current malignancies (excluding nonmelanoma skin cancers or carcinoma in situ of the cervix that has been adequately treated)
2) Pregnant women or nursing mothers
3) Any of the following hematologic abnormalities: WBC < 2500/mm3; platelets < 150,000/mm3; hemoglobin < 10 g/dL
4) Serologic evidence of infection with human immunodeficiency virus (HIV) or hepatitis B or C virus (HBV, HCV)
5) Presence of obstructive symptoms, confirmed by endoscopy showing an impassable stricture or computed tomography (CT) or barium studies showing stricture with prestenotic bowel dilation, within 6 months prior to receiving study drug
6) Likely to require surgery in the next 6 months, such as those with clinically apparent abscesses or severely symptomatic stenoses (patients with fistula abscesses and/or setons at screen may be eligible for study entry if abscesses can be drained before patients receive study drug)
7) Serious infections, particularly those of viral etiology, eg, known active CMV colitis, and who have history of opportunistic infections within the past year
8) Active infections that require antibiotic therapy (not to include use of antibiotics to manage CD)
9) Serious infections that required IV antibiotic therapy or hospitalization within 8 weeks prior to receiving study drug
10) Started, or have had a dose change of, sulfasalazine; 5-aminosalicylic acid (5-ASA); or antibiotics, probiotics, or topical therapies for CD within 2 weeks prior to receiving study drug
11) Had an increased dose in corticosteroid medication within 2 weeks prior to receiving study drug; is receiving IV steroids; or, is receiving a daily dose of > 40 mg prednisone, > 9 mg budesonide, or equivalent
12) Received a live vaccine within 6 weeks prior to receiving study drug (patients may not receive a live vaccine during treatment or for 12 weeks after treatment with study drug)
13) Received any monoclonal antibodies (including infliximab) or investigational agents or biologics within 3 months prior to receiving study drug
14) Received cyclosporine or tacrolimus (FK506) within 4 weeks of receiving study drug
15) Had a dose change of or discontinued from 6-mercaptopurine, azathioprine, or methotrexate within 4 weeks prior to receiving study drug
16) Significant organ dysfunction, including cardiac, renal, liver, CNS, pulmonary, vascular, non-CD-related gastrointestinal, endocrine, or metabolic (eg, creatinine ≥1.6 mg/dL; ALT or AST ≥ twice the upper limit of normal (ULN); alkaline phosphatase ≥ 1.5 × ULN; history of myocardial infarction, congestive heart failure, or arrhythmias within 6 months prior to study entry).
17) History of lymphoproliferative disorder
18) History of tuberculosis (TB) or other mycobacteria infection, or chest x-ray positive for previous TB infection
19) History of thrombophlebitis or pulmonary embolus
20) Histories of immune deficiency or autoimmune disorders other than CD (not including joint, skin, hepatic, and ocular inflammatory conditions that may be components of CD)
21) History of seizure with subtherapeutic blood levels of anticonvulsive medication (documented) within one week before study enrollment.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary endpoint, which is determined by clinical examination, is clinical response, defined as external closure of at least 50% of perianal fistulas identified at baseline and observed at two consecutive study visits at least 4 weeks apart by Study Day 89, without an accompanying increase in dose(s) of concomitant medication(s) or the addition of new medication(s) as therapy for CD, or CD-related surgery. | |
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | 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) | 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 | No |
| E.8.1.1 | Randomised | No |
| 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | |
| 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 | | There are no predefined criteria for trial termination in this study. However, if PDL and/or the investigator(s) discover conditions during the course of the study that indicate it should be discontinued, an appropriate procedure for terminating the study will be instituted, including notification of the appropriate regulatory agencies and IRB or IEC at all study sites. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
