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 (MACS2163)

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.

Study Overview

• Status: Withdrawn
• Conditions: β-thalassemia Major
• Intervention / Treatment: Drug: Deferasirox

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 71 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deferasirox; 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; Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): April 1, 2014
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: November 6, 2012
• First Posted (Estimate): November 9, 2012

Study Record Updates

• Last Update Posted (Actual): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: deferasirox
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670ACN02