E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
iron overload in non-transfusion-dependent thalassemia patients |
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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 | 10043388 |
E.1.2 | Term | Thalassaemia |
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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 |
To assess the efficacy of two deferasirox doses (5 mg/kg/day and 10 mg/kg/day) in patients with non-transfusion-dependent thalassemia based on change in LIC from baseline after one year of treatment compared to placebo treated patients |
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E.2.2 | Secondary objectives of the trial |
To compare change in serum ferritin over one year of treatment with deferasirox or placebo To evaluate the relationship between serum ferritin and LIC To evaluate the safety of deferasirox in non-transfusion-dependent thalassemia patients To assess the change from baseline in hematological and iron metabolism parameters (e.g. hemoglobin, transferin saturation) To assess iron accumulation rate in non-transfusion-dependent patients treated with placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female aged ≥ 10 y with non-transfusion-dependent thalassemia syndromes, who has not received any transfusion within the previous 6 months prior to entry into the study LIC≥ 5 mg/g dw measured by R2 MRI at screening Serum ferritin > 300 ng/mL at screening (two consecutive values at least 14 days apart from each other) Written informed consent obtained prior to any screening procedures |
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E.4 | Principal exclusion criteria |
A known lifetime history of transfusion in excess of 20 PRBC HbSvariants of thalassemia syndromes Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) during the course of the study will not be excluded Any blood transfusion and chelation within the prior 6 months of study start Patients unable to undergo study assessments including MRI, e.g. who are claustrophobic to MRI, have a cardiac pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (Example: some types of aneurysm clips, shrapnel), and patients who are obese (exceeding the equipment limits) Significant proteinuria as indicated by a urine protein : urine creatinine ratio > 0.5 mg/mg in a non-first void urine sample at visit 1 or visit 2 (or alternatively in two of three samples obtained for screening) Creatinine clearance ≤ 60 ml/min on two measurements during visit 1 and visit 2 Serum creatinine > ULN on two measurements during visit 1 and visit 2 ALT >3 x ULN at visit 1 or visit 2 Clinical evidence of active hepatitis B (positive HBsAg with negative HBsAb) or hepatitis C (positive HCV antibody and detectable HCV RNA with ALT above the normal range) Known diagnosis of cirrhosis (confirmed by biopsy if available) Concomitant therapy with hydroxyurea, erythropoietin, butyrate A history of deferasirox treatment A history of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy History of positive HIV serology (ELISA or Western blot) Presence of a surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of the study drug Patients with active inflammatory diseases that may interfere with the accurate measurement of serum ferritin Pregnant or breast feeding patients, or patients of reproductive potential not employing an effective method of birth control Patients participating in another clinical trial or receiving a systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol History of hypersensitivity to any of the study drug or excipients Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.) Illicit drug use and/or alcohol use, defined as no more than one drink a day for women, and no more than two drinks a day for men within the 12 months prior to enrolment. A standard drink is generally considered to be 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in MRI-measured LIC from baseline at 12 months |
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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 | No |
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 | Yes |
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) | 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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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
| |
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 |