Chronic iron overload in patients with non-transfusion-dependent thalassemia MedDRA version: 9.1 Level: HLT Classification code 10043389 Term: Thalassaemic disorders
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core: •Male or female aged = 10 years [= 18 years for sites in Greece] with non-transfusion-dependent thalassemia syndromes, who has not received any transfusion within the previous 6 months prior to entry into the study • LIC= 5 mg Fe/g dw measured by R2 MRI at screening • Serum ferritin > 300 ng/mL at screening (two consecutive values at least 14 days apart from each other) • Written informed consent obtained prior to any screening procedures Extension: • Patients who completed the core CICL670A2209 clinical trial • Written informed consent obtained prior to entry into one year extension study Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Core: • Patients whose clinical condition allow phlebotomy • HbS–variants of thalassemia syndromes • Anticipated regular transfusion program during the study. • Any blood transfusion 6 months prior to study start • Chelation within 1 month prior to study treatment • Patients unable to undergo study assessments including MRI • Significant proteinuria • Creatinine clearance = 60 ml/min on two measurements during visit 1 and visit 2 • Serum creatinine > ULN on two measurements during visit 1 and visit 2 • ALT >5 x ULN at visit 1 and visit 2 • Clinical evidence of active hepatitis B or C • Known diagnosis of cirrhosis (confirmed by biopsy if available) • Concomitant therapy with hydroxyurea, erythropoietin, butyrate • Prior deferasirox treatment • History of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy • History of positive HIV serology (ELISA or Western blot) • Presence of a surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of the study drug • Active inflammatory diseases that may interfere with the accurate measurement of serum ferritin • Pregnancy, breast feeding, patients of reproductive potential not employing an effective method of birth control • Paticipationn another clinical trial or receiving a systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days • Hstory of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol • Hstory of hypersensitivity to any of the study drug or excipients • Significant medical condition interfering with the ability to partake in this study • History of drug or alcohol abuse within the 12 months prior to enrollment • Body weight < 20 kg Extension: Please see protocol Post-text Supplement 2 for details
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Core: To compare the efficacy of two regimens of deferasirox administration (starting doses of 5 and 10 mg/kg/day) in patients with non-transfusion-dependent thalassemia based on change in LIC from baseline after one year of treatment compared to placebo treated patients. Extension: To evaluate the number of patients reaching LIC<5mg Fe/g dw and to evaluate the long-term safety of deferasirox administration in patients with non-transfusion-dependent thalassemia ; Secondary Objective: • To compare the efficacy of two regimens of deferasirox administration (starting doses of 5 and 10 mg/kg/day) based on change in LIC from baseline after 6 months of treatment compared to placebo-treated patients • To compare change in serum ferritin over one year of treatment with deferasirox or placebo • To evaluate the safety of both regimens of deferasirox versus placebo in non-transfusion-dependent thalassemia patients • To evaluate efficacy and safety of dose doubling • To evaluate the last LIC value under doubled dose to the last value of LIC before the doubling of the dose • To evaluate the relationship between serum ferritin and LIC • To assess the change from baseline in hematological and iron metabolism parameters (e.g. hemoglobin, transferin saturation) • To evaluate the iron accumulation rate based on LIC assessment in non-transfusion-dependent thalassemia patients treated with placebo. Extension: please see protocol post-text supplement 2 ;Primary end point(s): Change in mean liver iron concentration at end of study vs placebo | — |
Countries
Greece, Italy, United Kingdom
Outcome results
None listed