Clinical trial NCT00873041: Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study
Official title: A Randomized, Double-blind, Placebo-controlled, Phase II Study to Evaluate Efficacy and Safety of Deferasirox in Non-transfusion-dependent Thalassemia Patients With Iron Overload
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-transfusion Dependent Thalassemia
Keywords: Thalassemia
thalassemia intermedia
alpha-thalassemia
beta-thalassemia
deferasirox
iron overload
non-transfusion dependent
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-04-01
Enrollment: 166
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: CICL670A2209: This study will evaluate the safety and efficacy of deferasirox in non-transfusion dependent thalassemia patients with iron overload. Patients will be treated either with active treatment (deferasirox) or placebo for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study with the active treatment (deferasirox) in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the liver will be evaluated using magnetic resonance imaging (MRI) assessments.

CICL670A2209E1: A one-year open-label extension to a randomized, double-blind, placebo-controlled, phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload (Thalassa).


Eligibility criteria: Core Inclusion Criteria:

* Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
* Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
* Serum ferritin \>300 ng/mL at screening

Core Exclusion Criteria:

* Hemoglobin S (HbS)-variants of thalassemia syndromes
* Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded
* Any blood transfusion 6 months prior to study start
* Creatinine clearance ≤ 60 mL/min at screening
* Serum creatinine above the upper limit of normal at both screening visits
* Significant proteinuria as indicated by a urine protein/urine creatinine ratio \> 1.0 mg/mg
* Alanine aminotransferase (ALT) of \> 5 x the upper limit of normal at both screening visits
* Concomitant therapy with hydroxyurea, erythropoietin, butyrate
* History of deferasirox treatment
* Pediatric patients: a patient's weight of below 20 kg

Extension Inclusion Criteria:

* Patients who completed the core CICL670A2209 clinical trial
* Written informed consent obtained prior entry to one year extension study CICL670A2209

Extension Exclusion Criteria:

* Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and \> ULN who did not improve after drug interruption or dose reduction in the core study
* Patients with a continuous increase in ALT greater than 2 times the baseline value and \> 5 times ULN who did not improve after drug interruption or dose reduction in the core study
* Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study
* Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study
timeFrame: Core Baseline to End of Extension Study (up to 24 months)
Secondary outcomes:
measure: Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter
timeFrame: Baseline, (Day 286 to End of Study [Day 365])
measure: Core Study: Change in Serum Ferritin Between Baseline and Second Quarter
timeFrame: Baseline, (Day 106 to Day 195)
measure: Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
timeFrame: 52 Weeks
measure: Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24
timeFrame: Baseline, Week 24, Week 52
measure: Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
timeFrame: Baseline, 52 weeks
measure: Core Study: Change From Baseline in Hemoglobin at Month 12
timeFrame: Baseline, Month 12
measure: Core Study: Change From Baseline in Transferrin Saturation at Month 12
timeFrame: Baseline, Month 12
measure: Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
timeFrame: 52 Weeks
measure: Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure
timeFrame: Baseline, 52 Weeks
measure: Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure
timeFrame: Baseline, 52 Weeks
measure: Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate
timeFrame: Baseline, 52 Weeks
measure: Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter
timeFrame: Core Baseline, Eighth Quarter (last 3 months of the study)
measure: Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
timeFrame: Core Baseline, Month 24
measure: Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
timeFrame: Core Baseline, Month 24
measure: Extension Study: Change From Baseline in Hemoglobin at Month 24
timeFrame: Core Baseline, Month 24
measure: Extension Study: Change From Baseline in Transferrin Saturation at Month 24
timeFrame: Core Baseline, Month 24
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital/Division of Hematology/Oncology
state: Illinois
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Medical College of Cornell University
state: New York
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Rome
country: Italy
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Ampang Selangor
country: Malaysia
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Taher AT, Porter JB, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, Siritanaratkul N, Origa R, Karakas Z, Habr D, Zhu Z, Cappellini MD. Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia. Br J Haematol. 2015 Jan;168(2):284-90. doi: 10.1111/bjh.13119. Epub 2014 Sep 12.
citation: Taher AT, Porter JB, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, Siritanaratkul N, Galanello R, Karakas Z, Lawniczek T, Habr D, Ros J, Zhang Y, Cappellini MD. Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients. Am J Hematol. 2013 Jun;88(6):503-6. doi: 10.1002/ajh.23445. Epub 2013 May 13.