E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
•Beta-thalassemia
•Iron Overload
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054658 |
E.1.2 | Term | Thalassemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 |
Cardiac Iron in B thalassemia patients ( Time Frame: From baseline to week 25 and weeks 49 and 77 of the trial ) |
|
E.2.2 | Secondary objectives of the trial |
•Safety and tolerabilty of deferasirox [ Time Frame: throughout the study ]
•Changes in liver iron concentration (LIC) [ Time Frame: From baseline to week 25 and weeks 49 and 77 of trial ]
•Changes in ventricular ejection fraction [ Time Frame: From baseline to weeks 25, 49 and 77 ]
•Ferritin, NTBI (LPI and DCI)& iron metabolism parameters [ Time Frame: From Baseline through week 25, and weeks 49 and 77 of trial ]
•Compliance with deferasirox [ Time Frame: Throughout the study ] |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•- Male or female β-thalassemia outpatients on chronic transfusion therapy (defined as > 8 transfusions per year)
•Lifetime minimum of 100 previous packed red blood cell transfusions
•Patients currently on chelation therapy will require a one day wash out prior to the first dose of study drug
•Age ≥ 10 years
•Sexually active females of childbearing potential must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy.
|
|
E.4 | Principal exclusion criteria |
•Ejection Fraction < 56 % measured using steady-state free precession imaging by MRI
•Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia
•Abnormal laboratory values as defined by the protocol
•Clinical or laboratory evidence of active Hepatitis B or Hepatitis C
•History of HIV positive test result (ELISA or Western blot)
•Uncontrolled systemic hypertension
•Second or third degree A-V block
•Life-threatening arrhythmias, including sustained ventricular tachycardia and aborted sudden death, within the last year
•History of cardiac conditions or unstable cardiac disease not controlled by standard medical therapy
•History of clinically relevant ocular toxicity related to iron chelation
•Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
•Pregnancy or breast feeding (documented negative pregnancy test required for study entry)
•Patients enrolled in an ongoing clinical trial of deferasirox (ICL670) cannot be withdrawn in order to participate in this study
•Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days
•Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
•History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative
•Other inclusion/exclusion criteria may apply
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|
E.5 End points |
E.5.1 | Primary end point(s) |
Cardiac Iron in B thalassemia patients |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 25 and weeks 49 and 77 of the trial |
|
E.5.2 | Secondary end point(s) |
•Safety and tolerabilty of deferasirox
•Changes in liver iron concentration (LIC)
•Changes in ventricular ejection fraction
•Ferritin, NTBI (LPI and DCI)& iron metabolism parameters
•Compliance with deferasirox |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Safety and tolerabilty of deferasirox: throughout the study
•Changes in liver iron concentration : From baseline to week 25 and weeks 49 and 77 of trial
•Changes in ventricular ejection fraction: From baseline to weeks 25, 49 and 77
•Ferritin, NTBI (LPI and DCI)& iron metabolism parameters : From Baseline through week 25, and weeks 49 and 77 of trial
•Compliance with deferasirox: Throughout the study |
|
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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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
|
November 2009 (final data collection date for primary outcome measure) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |