A 4-year Extension Study to Core 1-year Study of Iron Chelation Therapy With Deferasirox in β-thalassemia Major Pediatric Patients With Transfusional Iron Overload.

A 4-year Extension to a Phase II a Multicenter Study Evaluating Long-term Safety, Tolerability, Pharmacokinetics and Effects on Liver Iron Concentration of Repeated Doses of 10 mg/kg/Day of Deferasirox in Pediatric Patients With Transfusion Dependent β-thalassemia Major.

In this 4-year extension study the safety, efficacy and and pharmacokinetics of deferasirox in regularly transfused pediatric patients with β-thalassemia major was assessed. Patients who successfully completed the main 1 year trial (NCT00390858) were eligible to continue in this extension trial and receive chelation therapy with deferasirox for up to 4 years.

Study Overview

• Status: Completed
• Conditions: Transfusional Iron Overload; β-thalassemia Major; Pediatric Rare Anemia
• Intervention / Treatment: Drug: Deferasirox

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Novartis Investigative Site
• Italy
  • Cagliari, Italy
    • Novartis Investigative Site
  • Genova, Italy
    • Novartis Investigative Site
  • Torino, Italy
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Completion of the planned 12-month core trial, (NCT00390858).
• Female patients who have reached menarche and who were sexually active were to use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.
• Written informed consent obtained from the patient, and/or from the parent or legal guardian in accordance with the national legislation.

Exclusion Criteria:

• Pregnant or breast feeding patients
• Patients with a history of non-compliance to medical regimens and patients who are considered by the investigator as potentially unreliable.

Other protocol-defined exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deferasirox; Initial dose of 10 mg/kg, dose modifications of ± 5 or 10 mg/kg were based on participant response.

Drug: Deferasirox; Deferasirox in children from 1 to 18 years old was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters and on increasing or decreasing Liver Iron Concentration (LIC), and serum ferritin. Deferasirox was available as 125 mg, 250 mg and 500 mg tablets.; Other Names: ICL670

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Adverse Events by Primary System Organ Class (SOC)	Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.	4 year extension + core 1 year
Change in Liver Iron Concentration (LIC)	Change in Liver Iron Concentration [LIC] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw)	Baseline of Core Study to End of Extension Study, up to 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Body Iron Elimination (TBIE) Rate (mg/kg/Day)	Total Iron Body Elimination (TBIE) Rate [mg/kg/Day] was calculated for each patient based on SQUID ( Superconducting Quantum Interference Device) results.	Baseline of Core Study to End of Extension Study, up to 5 years
Relative Change in Serum Ferritin Level	Serum levels were drawn at the baseline of the Core Study up to 18 months of the Extension Study. Levels were analyzed for serum ferritin measured in micrograms per Liter. Relative change (%) in serum ferritin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in ferritin level from Baseline/Baseline level) x 100.	Baseline of Core Study to Extension 18 months, up to 2.5 years.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Dr. Gianluca Forni, Novartis Pharmaceuticals; Study Director: Prof. Renzo Galanello, Novartis Pharmaceuticals; Study Director: Prof. Antonio Piga, Novartis Pharmaceuticals; Study Director: Dr. Yves Bertrand, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: October 18, 2006
• First Submitted That Met QC Criteria: October 19, 2006
• First Posted (Estimate): October 20, 2006

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: February 12, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: iron overload; deferasirox; β-thalassemia major; pediatric rare anemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Iron Overload; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670A0106E1