E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transfusional iron overload |
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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 |
To evaluate if starting doses of ICL670, based on transfusion history, and subsequent dose titration can provide clinically acceptable chelation, as measured by serum ferritin, to patients presenting with transfusional hemosiderosis and pre-existing serum ferritin levels of ≥ 1000 ng/ml or patients presenting with serum ferritin <1000 ng/ml, but with history of multiple transfusions (>20 transfusions or 100ml/kg of packed red blood cells) and LIC > 2mg Fe/g dw (as confirmed by R2-MRI). Clinically acceptable chelation will be assessed by comparison of serum ferritin at baseline vs 52 weeks of treatment with ICL670. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the safety and tolerability of ICL670 given for up to 52 weeks • Evaluate efficacy (LIC maintenance, relation between serum ferritin and LIC), tolerability and safety in the subgroup of patients with baseline LIC<7 mg Fe/g dw • Evaluate the relationship between serum ferritin and potential surrogate markers • Evaluate dose adjustment regimens as dictated by efficacy and safety parameters in comparison to transfusional burdens. • Evaluate efficacy and safety by underlying condition • Assess drug usage compliance • Evaluate the impact of iron chelation therapy on quality of life • Evaluate patient satisfaction with ICL670 • Evaluate the change in LIC via non-invasive R2-MRI and the relationship between LIC and serum ferritin. • Evaluate cardiac iron overload and cardiac function in a substudy in 85 patients aged ≥ 10 years
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CICL 670 A2409 E1: A 18 month extension to ICL670A2409 an open label, single arm multi centre trial evaluating the efficacy and safety of oral ICL670 (20 mg/kg/day) in patients diagnosed with transfusional dependent iron overload Objective: to extend treatment in study 2409 by and 18 months (Amdts 3 and 5). Extension not running in UK.
Post Text Supplements 8, 10 and 11: Cardiac Substudy Introduced by Amdt 2, extended by 1yr by Amdt 6 and a further 1yr by Amdt 7 (total treatment duration of 3 years). Objective: to evaluate the long term efficacy, safety and tolerability profile of ICL670 treatment in patients with cardiac oveload. |
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E.3 | Principal inclusion criteria |
• Patients presenting with transfusion-related iron overload (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml, or with serum ferritin <1000ng/ml, but with history of multiple transfusions (>20 transfusions or 100ml/kg of packed red blood cells) and LIC > 2mg Fe/g dw (as confirmed by R2-MRI). •age ≥ 2 years • Adult patients: written informed consent • Pediatric patients: written informed consent by their parents or legal guardians on the patient’s behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.
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E.4 | Principal exclusion criteria |
• non-transfusion-related hemosiderosis • clinical evidence supporting the need of intensive chelation • mean levels of alanine aminotransferase (ALT) > 300 U/l • uncontrolled systemic hypertension • serum creatinine above the upper limit of normal (ULN) • history of nephrotic syndrome • history of clinically relevant ocular toxicity related to iron chelation • systemic diseases which would prevent the patient from undergoing study treatment • psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment • pregnant or breastfeeding patients • treatment with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days • any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug • history or likelihood of non-compliance to medical regimens • history of drug or alcohol abuse within the past 12 months or evidence of such abuse during the run-in period • positive test to HIV •life expectancy of < 1year • pediatric patients only: body weight which prevents the use of the smallest tablet strength (125 mg) for proper dosing |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in serum ferritin from baseline vs. 52 weeks of treatment. If no 52 week serum ferritin value is present then comparison will be between baseline and the last observation. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Cardiac iron load and function (substudy) |
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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) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
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 | 98 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 |