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
Overview
- Phase
- Phase 2
- Intervention
- Deferasirox DT formulation
- Conditions
- Transfusion-dependent Anemia
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 224
- Locations
- 6
- Primary Endpoint
- Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent/assent before any study-specific procedures. Consent will be obtained from parent(s) or legal guardians. Investigators will also obtain assent of patients according to local guidelines.
- •Male and female children and adolescents aged ≥ 2 and \< 18 years. \[France: Male and female children and adolescent aged ≥ 2 and \< 18 years old, however children aged ≥ 2 and ≤ 6years can be enrolled only when deferoxamine treatment is contraindicated or inadequate in these patients as per investigator decision. Applicable to core phase only. Once in the core phase patients can turn 18 years and still be considered eligible, also for participation in the optional extension phase.
- •Any transfusion-dependent anemia associated with iron overload requiring iron chelation therapy and with a history of transfusion of approximately 20 PRBC units and a treatment goal to reduce iron burden (300mL PRBC = 1 unit in adults whereas 4 ml/kg PRBC is considered 1 unit for children).
- •Serum ferritin \> 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
- •Patient has to have participated and completed the 48 weeks core phase treatment as per protocol (For optional extension phase eligibility only).
Exclusion Criteria
- •Creatinine clearance below the contraindication limit in the locally approved prescribing information (using Schwartz formula) at screening visit 1 or screening visit
- •Serum creatinine \> 1.5 xULN at screening measured at screening Visit 1 and or screening Visit 2
- •ALT and/or AST \> 3.0 x ULN at screening visit 1 or screening visit 2..
- •Liver disease with severity of Child-Pugh class B or C.
- •Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 mg/mg in a second morning urine sample at screening Visit 1 or screening Visit
- •Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- •Direct (conjugated) bilirubin \>2 x ULN at screening visit 1 or screening visit
- •Local access to new formulation (granules or FCT) is available (For optional extension phase eligibility only).
- •Other protocol-defined Inclusion/Exclusion may apply.
Arms & Interventions
DFX DT
Participants will be administered deferasirox dispersible tablets orally once daily based on body weight for 48 weeks.
Intervention: Deferasirox DT formulation
DFX Granule
Participants will be administered deferasirox granules orally once daily in the form of stick packs based on body weight for 48 weeks.
Intervention: Deferasirox granule formulation
Outcomes
Primary Outcomes
Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase
Time Frame: 24 weeks
Compliance was calculated as the ratio of total count consumed to total count prescribed of deferasirox granule stick packs or dispersible tablets, where total count consumed was derived from cumulative dispensed, returned and lost/wasted counts over 24 weeks of treatment and total count prescribed was derived from cumulative prescribed count over 24 weeks of treatment.
Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase
Time Frame: From Baseline to Week 25
The analysis included the comparison of means between the two treatment arms of change from baseline after 24 weeks of treatment in serum ferritin in pediatric ICT naïve participants with iron overload. The endpoint was assessed at Week 25 visit.
Secondary Outcomes
- Percentage of Overall Compliance Using Stick Pack or Tablet Counts in ICT-naïve Participants During the Core Phase(48 weeks)
- Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase(From Baseline to 48 weeks)
- Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in Pre-treated Participants During the Core Phase(From Baseline to Week 25 and Week 48)
- Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Patient Reported Outcomes (PRO) Questionnaires(At Week 2, Week 3, Week 25 and Week 48)
- Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Caregiver's Perspective)(At Week 2, Week 3, Week 25 and Week 48)
- Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Child's Perspective)(At Week 2, Week 3, Week 25 and Week 48)
- Change Over-time in Domain Score of Palatability Using Patient Reported Outcomes (PRO) Questionnaires(At Week 2, Week 3, Week 25 and Week 48)
- Change Over-time in Domain Score of Palatability Using Observer Reported Outcomes (ObsRO) Questionnaire(At Week 2, Week 3, Week 25 and Week 48)
- Change Over Time in Weekly Dose Violation Rate Using Compliance Patient Reported Outcomes (PRO) Questionnaire(At Week 1, Week 13, Week 25, Week 37 and Week 48)
- Change Over Time in Weekly Dose Violation Rate Using Compliance Observer Reported Outcomes (ObsRO) Questionnaire(At Week 1, Week 13, Week 25, Week 37 and Week 48)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Core Phase(From Baseline to 48 weeks)
- Pre-dose Concentrations of Deferasirox to Support the Assessment of Compliance(At Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45)
- Concentrations of Deferasirox Between 2 and 4 Hours Post-dose at Weeks 5 and 9(At Week 5 and Week 9)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Entire Granule Period(From Baseline to 305 weeks)
- Number of Participants With Adverse Events of Special Interest (AESI) During the Entire Granule Period(From Baseline to 305 weeks)