Phase 2
Completed N=224
Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload
Transfusion-dependent Anemia
Source: ClinicalTrials.gov NCT02435212 ↗
Enrolled (actual)
224
Serious AEs
25.1%
Results posted
Sep 2024
Primary outcomePrimary: Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase — 89.45; 91.78 percentage of compliance — p=0.3598
Summary
This was 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 dispersible tablet (DT) formulation in children and adolescents aged ≥ 2 and < 18 years at enrolment with any transfusion-dependent anemia requiring chelation therapy due to iron overload, to demonstrate the effect of improved compliance on iron burden.
Randomization was stratified by age groups (2 to <10 years, 10 to <18 years) and prior iron chelation therapy (Yes/ No). There were two study phases which include a 1 year core phase where participants were randomized to a 48 week treatment period to either Deferasirox DT or granules, and an optional extension phase where all participants received the granules up to 5 years. Participants who demonstrated benefit to granules or DT in the core phase, and/or expressed the wish to continue in the optional extension phase on granules, were offered this possibility until there was local access to the new formulation (granules or film-coated tablet (FCT)) or up to 5 years, whichever occurred first.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase |
89.45; 91.78 | 0.3598 |
| PRIMARY Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase |
305.8; 317.0 | — |
| SECONDARY Percentage of Overall Compliance Using Stick Pack or Tablet Counts in ICT-naïve Participants During the Core Phase |
91.57; 94.80 | — |
| SECONDARY Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase |
305.8; 317.0 | — |
| SECONDARY Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in Pre-treated Participants During the Core Phase |
59.0; 150.3; 207.7; 215.7 | — |
| SECONDARY Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Patient Reported Outcomes (PRO) Questionnaires |
9.5; 7.6; 10.9; 6.6; 11.9; 9.2 | — |
| SECONDARY Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Caregiver's Perspective) |
7.7; 5.8; 7.8; 5.8; 7.1; 6.5 | — |
| SECONDARY Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Child's Perspective) |
12.1; 8.2; 11.7; 8.2; 11.1; 9.1 | — |
| SECONDARY Change Over-time in Domain Score of Palatability Using Patient Reported Outcomes (PRO) Questionnaires |
8.8; 10.3; 9.6; 10.9; 9.2; 10.4 | — |
| SECONDARY Change Over-time in Domain Score of Palatability Using Observer Reported Outcomes (ObsRO) Questionnaire |
8.9; 10.9; 9.4; 10.8; 9.3; 10.6 | — |
| SECONDARY Change Over Time in Weekly Dose Violation Rate Using Compliance Patient Reported Outcomes (PRO) Questionnaire |
26.86; 26.79; 12.78; 23.41; 13.19; 25.93 | — |
| SECONDARY Change Over Time in Weekly Dose Violation Rate Using Compliance Observer Reported Outcomes (ObsRO) Questionnaire |
18.80; 27.79; 10.38; 18.65; 7.79; 13.72 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Core Phase |
108; 100; 23; 27 | — |
| SECONDARY Pre-dose Concentrations of Deferasirox to Support the Assessment of Compliance |
2.93; 1.40; 14.2; 11.8; 14.4; 11.7 | — |
| SECONDARY Concentrations of Deferasirox Between 2 and 4 Hours Post-dose at Weeks 5 and 9 |
65.2; 53.2; 70.4; 59.8 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Entire Granule Period |
64; 106; 48; 73; 22; 38 | — |
| SECONDARY Number of Participants With Adverse Events of Special Interest (AESI) During the Entire Granule Period |
52; 79; 3; 4; 5; 5 | — |
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 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 2.
- 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 2.
- 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 2.
- Local access to new formulation (granules or FCT) is available (For optional extension phase eligibility only).
Data sourced from ClinicalTrials.gov (NCT02435212). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.