E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
myelodysplastic syndromes(low/int-1 risk) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019613 |
E.1.2 | Term | Hemosiderosis |
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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 |
The primary objective is to compare deferasirox to placebo with regard to event-free survival (a composite primary endpoint including death and non-fatal events related to cardiac and liver function) in low and int-1 risk MDS patients with transfusional iron overload. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective is to compare overall survival. The other secondary objectives are to evaluate: -Change in endocrine function (thyroid and glycemic control) -Change in hematological function (MDS progression, transfusion requirements, and acute leukemia onset) -Change in serum ferritin level -Change in cardiac function Safety, in particular to assess the levels of increased risk for pre-specified adverse events (renal dysfunction, neutropenia, thrombocytopenia, gastrointestinal bleeding, and laboratory abnormalities) that would be clinically unacceptable in the context of the level of benefit that is likely to be provided by iron chelation using deferasirox in MDS patients with iron overload |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female patients, ≥18 years of age -Patient must weigh between 45-120 kg -Patients with low or intermediate (int-1) risk MDS, as determined by IPSS score. This must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable. Ferritin > 1000 mcg/L and < 2500 mcg/L at screening History of transfusion of 20 to 50 PRBC units Chelation-na�ve patients Anticipated to be transfused at least 8 times annually during the study -Sexually active pre-menopausal female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation |
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E.4 | Principal exclusion criteria |
-More than 3 years since diagnosis of MDS -Creatinine Clearance <40 ml/min -Serum creatinine > ULN at screening -Significant proteinuria as indicated by a urinary protein/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) -ECOG performance status > 2 -Left ventricular ejection fraction < 55% by echocardiography -A history of hospitalization for congestive heart failure -Systemic diseases which would prevent study treatment (e.g.uncontrolled hypertension,cardiovascular, renal, hepatic, metabolic, etc.) -Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range) -History of HIV positive test result (ELISA or Western blot) -Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start ALT or AST > 2.5 � ULN at screening -Total bilirubin > ULN at screening Diagnosis of liver cirrhosis Patients participating in another clinical trial or receiving an investigational drug -Patients with a history of another malignancy within the past five years, with the exception of basel skin carcinoma or cervical carcinoma in situ. -History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative -Presence of a surgical or medical condition which might significantly alter the absorption,distribution, metabolism or excretion of study drug -Pregnant, intending-to-become pregnant, or breast-feeding patients -History of drug or alcohol abuse within the 12 months prior to enrollment Patients who are found to be ineligible after screening procedures will have this documented on the screening log. These patients will not need to complete the end of study assessments. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite primary endpoint (event-free survival) defined as time from date of randomization to either death or any of the following non-fatal events: 1. Echocardiographic evidence of worsening cardiac function 2. Hospitalization for congestive heart failure 3. Liver function impairment 4. Liver cirrhosis |
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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 | 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) | Yes |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | 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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |