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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Iron Overload
• Intervention / Treatment: Drug: Deferasirox; Drug: Deferasirox

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Italy
  • Cagliari, Italy
    • Novartis Investigative Site
  • Genova, Italy
    • Novartis Investigative Site
  • Milan, Italy
    • Novartis Investigative Site
  • Torino, Italy
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox; 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; 10 mg/kg or 30 mg/kg orally daily; Drug: Deferasirox; 5 mg/kg or 30 mg/kg orally daily
Experimental: Deferasirox Crossover; 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; 10 mg/kg or 30 mg/kg orally daily; Drug: Deferasirox; 5 mg/kg or 30 mg/kg orally daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 16, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Estimate): August 11, 2011
• Last Update Submitted That Met QC Criteria: July 18, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: iron overload; B-thalassemia; iron chelation therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Overload; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670A0105E2