Extension Study of the Efficacy and Safety of Deferasirox Treatment in Beta-thalassemia Patients With Transfusional Hemosiderosis (Study Amended to 2-year Duration) (ESCALATOR)

1-year Extension to CICL670A2402 an Open-label, Multi-center Trial of the Efficacy and Safety of Long-term Treatment With Deferasirox (10 to 20 mg/kg/Day) in Beta-thalassemia Patients With Transfusional Hemosiderosis (Study Amended to 2- Year Duration)

To allow patients treated with deferasirox in the core study to continue iron chelation therapy for 2 years or until the drug became locally commercially available. To evaluate the long-term safety and efficacy of deferasirox by measuring treatment success, change in liver iron content (LIC) and change in serum ferritin levels. Safety was mainly assessed by incidence of adverse events (AEs)and clinically significant lab parameters.

Study Overview

• Status: Completed
• Conditions: Iron Overload; Hemosiderosis; Beta-thalassemia Major; Rare Anemia
• Intervention / Treatment: Drug: Deferasirox

Detailed Description

Iron accumulation is an inevitable consequence of chronic blood transfusions and results in serious complications in the absence of chelation treatment to remove excess iron. Deferasirox (Exjade, ICL670) is an oral chelator with high iron-binding potency and selectivity. This extension study aimed at collecting efficacy and safety data during 2 years of treatment with deferasirox in the extension study or until deferasirox became commercially available in the countries where the centers were located, whichever came first. The population comprised of β-thalassemia patients with transfusional hemosiderosis who could not be satisfactorily treated with deferoxamine or deferiprone.

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon
    • Novartis Investigative Site
• Oman
  • Muscat, Oman
    • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Novartis Investigative Site
• Syrian Arab Republic
  • Damascus, Syrian Arab Republic
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients completing the planned 12-month core study (NCT00171171)
• Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation
• Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation

Exclusion Criteria:

• Pregnant or breast feeding patients.
• Patients being considered by the investigator potentially unreliable and/or not cooperative with regard to the core study protocol, or the planned extension protocol

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

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox; Deferasirox was given orally once daily (10 to 20 mg/kg) to participants 2 years and older based on participant's body weight.	Drug: Deferasirox; Deferasirox was administered orally once daily. Deferasirox was available as 125 mg, 250 mg, and 500 mg tablets.; Other Names: Exjade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age	Success was defined as the percentage of participants with decreased liver iron content (LIC) at the end of extension study compared to core baseline (BL) LIC. Success Criteria: For participants with Baseline LIC from 1 - <7 mg Fe/g dw, success was achieved if LIC level maintained at 1 - <7 mg Fe/g dw. For participants with Baseline LIC ≥7 - <10 mg Fe/g dw, success was achieved if LIC dropped to between 1 and < 7 mg Fe/g dw. For participants with Baseline LIC ≥10 mg Fe/g dw, success was achieved if LIC dropped by at least 3 mg Fe/g dw. LIC was measured by biopsy or magnetic resonance imaging.	From Core Study Baseline, to Extension End of Study, Up to 3 Years
Absolute Change in Liver Iron Concentration (LIC)Measured by Liver MRI or Liver Biopsy From Core Study Baseline (BL) to End of Extension Study, by LIC Category	Liver MRI or Liver Biopsy was performed at the core study baseline (BL) and then 1 year and 2 years in the core study, baseline of the extension study and time of discontinuation from the extension visit (end of study). Liver iron content (LIC) is reported in milligram Iron per gram dry weight (mg Fe/g dw). Absolute change in LIC from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw.	From Baseline of Core Study to End of Extension Study, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Serum Ferritin Level Measured From Core Study Baseline (BL) to End of Extension Study	Serum Levels were assessed at core study baseline (BL), 1 year, 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study) in monthly intervals. Serum Ferritin is reported in micrograms per Liter (µg/L).	From Baseline of Core Study to End of Extension Study, up to 3 years
Absolute Change in Serum Ferritin Level for All Participants Measured From Core Study Baseline (BL) to End of Extension Study, by Baseline Liver Iron Content (LIC)	Serum Levels were assessed at core study baseline (BL) and then 1 year and 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study). Serum Ferritin is reported in micrograms per Liter. Absolute change in Serum Ferritin from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw.	From Baseline of Core Study to End of Extension Study, up to 3 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): August 31, 2011
• Last Update Submitted That Met QC Criteria: August 28, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: iron overload; Transfusional hemosiderosis; Deferasirox; Beta-thalassemia major; rare anemia; iron overload due to transfusion
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Metal Metabolism, Inborn Errors; Iron Overload; Thalassemia; beta-Thalassemia; Hemochromatosis; Hemosiderosis; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670A2402E1