Safety and Efficacy of Deferasirox in Patients With Transfusion Dependent Iron Overload - a Non-comparative Extension Study

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and the effects on liver iron of Deferasirox when given for a long treatment period in patients with transfusion dependent iron overload.

Official Title
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A 5-year Open Label, Non-comparative Extension to a Randomized, Open-label, Phase IIa Study to Evaluate Safety, Tolerability and the Effects on Liver Iron Concentration of Repeated Doses of 10 and 20 mg/kg/Day of Deferasirox in Comparison With 40 mg/kg/Day Deferoxamine in Patients With Transfusion-dependent Iron Overload

Conditions
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Liver Iron Overload

Intervention / Treatment
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* Drug: Deferasirox
* Drug: Deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients Currently participating in the 9-month comparative prolongation of extension phase of the original study. Patients currently participating in the food-effect sub-study, according to amendment 3. Ability to provide written informed consent prior to participation in this non-comparative extension study. Female patients sexually active must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation. Body weight of at least 35 kg. Exclusion Criteria: Pregnant or breastfeeding patients. History of non-compliance to medical regimens and patients who are considered potentially unreliable. Proteinuria > 300 mg/L second void morning urine. Patients with serum creatinine above the upper limit normal. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox<br>Deferasirox group consists of all participants who were initially randomized to 10 and 20 mg/kg/day deferasirox orally daily in the main study and remained on the same treatment during the comparative prolongation study (NCT00379483) and at the beginning of the 5-year non-comparative study | Drug: Deferasirox<br>* 10 mg/kg or 30 mg/kg orally daily<br>|
| Experimental: Deferasirox Crossover<br>Deferasirox Crossover group consists of participants who were initially randomized to 40 mg/kg/day deferoxamine (DFO)subcutaneously in the main study and comparative prolongation study and crossed over to 5mg/kg/day to 30 mg/kg/day deferasirox orally daily at the beginning of the 5-year non-comparative extension study | Drug: Deferasirox<br>* 5 mg/kg or 30 mg/kg orally daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox | The mean percentage change in liver iron content (LIC) as assessed by superconducting quantum interference device (SQUID) was evaluated by comparing the LIC at the start of Deferasirox treatment to the LIC at the end of the 5 year extension study for participants who were treated with Deferasirox for more than 3.5 years. LIC is expressed in milligrams of iron per gram of liver dry weight (mgFe/g dw). Relative change = 1- (Change in LIC from Baseline/Baseline level) x 100. | Baseline to 7 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change in Serum Ferritin From Baseline to 3.5 Years | The mean percentage change in serum ferritin was evaluated by comparing the serum ferritin level at the start of Deferasirox treatment to the serum ferritin level collected 18 months following the start of the extension study. Serum ferritin is measured in micrograms per Liter. Relative Change = 1- (Change in ferritin level from Baseline/Baseline level) x 100. | Baseline to 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron overload, iron chelation therapy, B-thalassemia