An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old

Study Overview
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Brief Summary
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To characterize the PK of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old, when administrated with a fixed starting dose of 20 mg/kg/day.

Official Title
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An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old

Conditions
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β-thalassemia Major

Intervention / Treatment
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* Drug: Deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients aged from 2 to less than 6 years old. Patients with transfusion dependent β-thalassemia major. Serum ferritin values ≥ 1000 ng/ml at screening. Written informed consent must be obtained from the patient's legal guardian in accordance with local law and regulation prior to any screening procedures. Exclusion Criteria: Non-transfusion-dependent thalassemia. Systemic diseases which would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.) Serum creatinine > age adjusted ULN. Significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥ 0.5mg/mg in a non-first void urine sample at screening. If UPCR is found to be ≥ 0.5 mg/mg the test can be repeated after 1 month. ALT/AST > 2.5xULN and total bilirubin > 1×ULN. Left ventricular ejection fraction < 56% by echocardiography. Patient has a known history of HIV seropositivity or history of active/treated hepatitis B or C (a test for screening is not required). A history of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy Any surgical or medical conditions which will significantly alter the absorption, distribution, metabolism or excretion of the drug(e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection). Other conditions which investigator deems potential harm to patients if participate the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 71 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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox<br>The study will provide PK, safety, tolerability and efficacy data collected during 48 weeks of treatment with deferasirox in Chinese pediatric patients with transfusion dependent -thalassemia major, aged 2 to <6 years at enrollment. The target patient pool consists of 20 patients with evidence of iron overload measured by serum ferritin level at the start of study. Patients will start their deferasirox treatment with a dose of 20 mg/kg/day. Serum ferritin will be monitored every month and the dose of deferasirox will be adjusted if necessary every 3 months based on the trends in serum ferritin. Other possible dose adjustments will be based on the patient's safety assessments. | Drug: Deferasirox<br>* Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old. | Area under the plasma concentration-time curve from time zero to the end of the dosing interval. | PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. | 
| the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Cmax | The maximum plasma concentration of study medication. | PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. | 
| the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Tmax | Tmax was directly determined from the raw plasma concentration-time data. | PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of deferasirox following multiple dosing in pediatric β-thalassemia major patients. | The adverse events and abnormal measurements of hematology, blood chemistry, urinalysis, urinary protein/creatinine ratio, physical examination, auditory and ocular examinations, ECG, ECHO, and growth development are collected for the measurement of safety and tolerability. | Baseline, every 4 weeks until 48 weeks after taking the drug | 
| The efficacy of deferasirox in pediatric β-thalassemia patients as measured by change of serum ferritin. | Changes in serum ferritin from baseline to every 4 weeks are collected for the measurement of efficacy. | Baseline, every 4 weeks until 48 weeks after taking the drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deferasirox