Study to evaluate treatment compliance, efficacy and safety of an improved deferasirox formulation (granules) in pediatric patients (2-<18 years old) with iron overload

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2013-004739-55-HU
• Date of registration: 25/07/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study to evaluate treatment compliance, efficacy and safety of an improved deferasirox formulation (granules) in pediatric patients (2-<18 years old) with iron overload
• Scientific 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
• Date of first enrolment: 20/09/2016
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004739-55
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: optional extension phase with granules after core phase If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, China, Colombia, Denmark, Egypt, France, Hungary, India, Italy, Lebanon, Malaysia, Oman, Panama, Philippines, Russian Federation, Thailand, Tunisia, Turkey, United Arab Emirates, United States

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent/assent before any study-specific procedures. Consent will be obtained from parent(s) or legal guardians. Investigators will also obtain consent/assent of patients according to local guidelines.
2. 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
3. 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).
4. Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 for inclusion in the core phase or Visit 16 and Visit 777
for inclusion in the extension phase (the mean value will be used for eligibility criteria).
5. Patient has to have participated and completed the 48 weeks core phase treatment as per protocol (For optional extension phase eligibility only).
6. Patient needs to meet all the eligibility criteria (inclusion and exclusion) as defined in the core phase at Visit 17 (For optional extension phase eligibility only).

Are the trial subjects under 18? yes
Number of subjects for this age range: 240
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Creatinine clearance below the contraindication limit in the locally approved prescribing information (using the Schwartz formula) at screening Visit 1 , screening Visit 2, Visit 16 or Visit 777
2. Serum creatinine > 1.5 xULN at screening Visit 1 , screening Visit 2, Visit 16 or Visit 777
3. ALT and/or AST > 3.0 x ULN at screening Visit 1 , screening Visit 2, Visit 16 or Visit 777
4. Liver disease with severity of Child-Pugh class B or C.
5. Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a second morning urine sample at screening Visit 1, screening Visit 2, Visit 16 or Visit 777
6. 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).

Other exclusion criteria as per full protocol may apply.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

transfusion-dependent anemia requiring chelation therapy due to iron overload
MedDRA version: 20.0 Level: LLT Classification code 10074295 Term: Transfusion dependent anemia System Organ Class: 100000012844

Intervention(s)

Trade Name: Exjade
Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Trade Name: Exjade
Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Exjade
Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Granules
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-

Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Granules
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 180-

Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Granules
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 360-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. 48 weeks
2. baseline and 48 weeks

Main Objective: 1. To evaluate both formulations on patient compliance, using stick pack/tablet count in ICT naive patients during core phase
2. To evaluate the change from baseline in serum ferritin at 48 weeks of treatment for both formulations in ICT naive patients

Secondary Objective: Core phase
1. to evaluate both formulations on serum ferritin in ICT naive and pretreated patients
2. To evaluate both formulations on patient satisfaction and palatability using Patient / Observer Reported Outcomes (PRO/ObsRO) questionnaires
3. To evaluate both formulations on overall safety
4. To evaluate compliance using a daily PRO/ObsRO questionnaire
5. To evaluate pre-dose PK data to support the assessment of compliance
6. Post-dose data to be analyzed along with pre-dose PK data

Extension phase:
to assess additional safety data about new formulation (granules) in paediatric population

Primary end point(s): 1. Compliance measured by stick pack/tablet count
2. Change from baseline in serum ferritin at 48 weeks of treatment

Secondary Outcome(s)

Secondary end point(s): Core phase:
1. Change from baseline in serum ferritin at 48 weeks of treatment
2. Domain scores of treatment satisfaction and palatability over time
3. Frequency of Adverse Events (AEs) as a measure of overall safety
4. Severity of Adverse Events (AEs) as a measure of overall safety
4. Rate of dosing instructions deviations
5. Pre-dose deferasirox concentrations in all patients [except Egypt]
6. Post-dose deferasirox concentrations between 2 and 4 hours postdose at Weeks 5 and 9 (2 samples)

Extension phase:
Overall safety, as measured by frequency and severity of adverse events (including 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, and growth and development evaluations will be assessed.

Timepoint(s) of evaluation of this end point: Core phase:
1. 48 weeks
2. 48 weeks
3. Baseline and 48 weeks
4. Baseline and 48 weeks
5. Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45
6. Week 5 and 9

Extension phase:
Week 309

Secondary ID(s)

CICL670F2202

2013-004739-55-BE

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 31/08/2016
Contact: