Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload
This is a randomized, open-label, multicenter, two arm, phase II study to evaluate treatment compliance and change in serum ferritin of a deferasirox granule formulation and a deferasirox DT formulation in children and adolescents aged ≥ 2 and < 18 years at enrollment with any transfusion-dependent anemia requiring chelation therapy due to iron overload, to demonstrate the effect of improved compliance on iron burden.
Randomization will be stratified by age groups (2 to <10 years, 10 to <18 years) and prior iron chelation therapy (Yes/ No). There will be two study phases which include a 1 year core phase where patients will be randomized to a 48 week treatment period to either Deferasirox DT or granules, and an optional extension phase where all patients will receive the granules up to 5 years. Patients who demonstrated benefit to granules or DT in the core phase, and/or express the wish to continue in the optional extension phase on granules, will be offered this possibility until there is local access to the new formulation (granules or FCT) or up to 5 years, whichever occurs first.
|Transfusion-dependent Anemia||Drug: Deferasirox granule formulation Drug: Deferasirox DT formulation||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Randomized, Open-label, Multicenter, Two Arm, Phase II Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients With Iron Overload|
- Compliance (using stick/pack tablet count). [ Time Frame: 48 weeks ]Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
- Change in serum ferritin in ICT naive patients. [ Time Frame: Baseline, 48 weeks ]The comparison of means between the two treatment arms of change from baseline to week 48 of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
- Domain scores of treatment satisfaction and palatability over time [ Time Frame: From baseline to 48 weeks ]To evaluate both formulations on patient satisfaction and palatability using Patient / Observer Reported Outcomes (PRO/ObsRO) questionnaires
- Overall safety, as measured by frequency and severity of adverse [ Time Frame: From Baseline to 48 weeks ]This includes active monitoring for renal toxicity; including renal failure, hepatic toxicity; including hepatic failure, and gastrointestinal hemorrhage), and changes in laboratory values from baseline (serum creatinine, creatinine clearance, ALT, AST, RBC and WBC). In addition, vital signs, physical, ophthalmological, audiometric, cardiac, and growth and development evaluations will be assessed.
- Rate of dosing instructions deviations ('Compliance', using a questionnaire) [ Time Frame: From Baseline to 48 weeks ]This includes doses missed/not taken at the same time every day, to evaluate the compliance using a daily PRO/ObsRO questionnaire.
- Pre-dose deferasirox concentrations in all patients [ Time Frame: at Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45 (13 samples) ]The pre-dose concentration by incident dose will be plotted for Week 1, Week 3, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29, Week 33, Week, 37, Week 41 and Week 45 based on data from all patients. Pre-dose PK data from all patients will be analyzed to support the assessment of compliance.Predicted individual concentrations derived from the compartmental model will be compared to respective observed pre-dose concentrations. Distributions of the difference between predicted and observed values will be shown graphically by boxplots for both treatment groups and visit.
- Post-dose deferasirox concentrations between 2 and 4 hours post-dose at Weeks 5 and 9 [ Time Frame: Week 5, Week 9 ]post-dose PK data to be analyzed along with pre-dose PK data
- Change in serum ferritin in ICT naïve and pretreated patients [ Time Frame: Baseline, 48 weeks ]To evaluate absolute and relative change from baseline in serum ferritin in both populations.
- PK/PD relationship [ Time Frame: From Baseline to 48 weeks ]To explore exposure-response relationships for measures of safety and effectiveness: serum creatinine change from baseline, notable serum creatinine values, serum creatinine clearance change from baseline and notable serum creatinine clearance categories, serum ferritin change from baseline, in relationship to derived PK parameters for pre- and post-dose deferasirox concentrations.
- Assess additional safety, as measured by frequency and severity of adverse for granules during extension phase [ Time Frame: From Baseline to 305 weeks ]This includesactive monitoring for renal toxicity; including renal failure, hepatic toxicity; including hepatic failure, and gastrointestinal hemorrhage), and changes in laboratory values from baseline (serum creatinine, creatinine clearance, ALT, AST, RBC and WBC). In addition, vital signs, physical, ophthalmological, audiometric, and growth and development evaluations will be assessed.
|Actual Study Start Date:||October 21, 2015|
|Estimated Study Completion Date:||December 29, 2023|
|Estimated Primary Completion Date:||December 29, 2023 (Final data collection date for primary outcome measure)|
|Active Comparator: Arm 1||
Drug: Deferasirox DT formulation
Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use
Other Name: Exjade, ICL670
|Experimental: Arm 2||
Drug: Deferasirox granule formulation
Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use.
Other Name: ICL670
Please refer to this study by its ClinicalTrials.gov identifier: NCT02435212
|Contact: Novartis Pharmaceuticalsfirstname.lastname@example.org|
|Contact: Novartis Pharmaceuticalsemail@example.com|
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|