E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with diagnosis of thalassemia major with iron overload or regularly transfused MDS patients (Low/Intermediate-1 IPSS risk and 1 year life expectancy) |
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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 | 10010329 |
E.1.2 | Term | Congenital anaemia |
|
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 determine the iron chelation therapy efficacy with deferasirox by total liver iron overload assessment using MID. |
|
E.2.2 | Secondary objectives of the trial |
Assessment of iron burden in abdomen (extra-hepatic site) through MRI Liver fibrosis assessment using FibroScan (EchoSens, Paris, France) Assessment of serum ferritin value Assessment of cardiac iron overload (MRI T2*) and cardiac function Evaluation of electric conductivity of abdominal tissues to quantify and differentiate hepatic steatosis in order to assess the influence on the drug efficacy Assessment of safety and tolerability of deferasirox treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of thalassemia major with iron overload or regularly transfused MDS patients (Low/Intermediate-1 IPSS risk and 1 year life expectancy) M/F adult patients (age ≥18 years) Patients starting/about to start or potentially eligible to the treatment with deferasirox according to locally approved label Female patients who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation Written informed consent by the patient in accordance with the national legislation |
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E.4 | Principal exclusion criteria |
Non transfusional hemosiderosis Renal impairment and/or with estimated creatinine clearance <60 ml/min at baseline Serum creatinine above the upper limit of normal range at screening Significant proteinuria as indicated by urinary protein/creatinine ratio &#8805; 1 in a non-first void urine sample at baseline History of nephrotic syndrome Severe liver impairment and/or ALT (SGPT) and AST (SGOT) >5 ULN Patients with uncontrolled systemic hypertension Pregnant or breast feeding patients Hypersensitivity to the active substance or to any of the excipients Concomitant use of other iron chelating agents History of clinically relevant ocular and auditory toxicity related to iron chelation therapy Heart function: Left Ventricular Ejection Fraction (LEF) <50% assessed by echo or <60% by MRI and/or T2* <10 ms measured in the last year Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment Patients unable to undergo study assessments including MRI and MID e.g. patients who are claustrophobic to MRI or have metallic prostheses not compatible with both MRI and MID procedures or patients who are obese (exceeding the equipment limits of MRI) Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days. Patients being treated with experimental drugs for MDS, including thalidomide or analogues, azacitidine in the previous four weeks. These patients are eligible after a minimum washout period of four weeks Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as the following: - history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding - history of major gastrointestinal tract surgery such as gastrectomy, gastro-enterostomy or bowel resection - history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase - history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN - history of urinary obstruction or difficulty in voiding History of drug or alcohol abuse Patients with positive test to HIV History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative Patient unwilling to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the iron chelation therapy efficacy with deferasirox by total liver iron overload assessment using MID. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |