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-BG
• Date of registration: 10/09/2015
• 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: 15/10/2015
• Target sample size: 216
• 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, Mexico, 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 (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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 216
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 or screening Visit 2
2. Serum creatinine > 1.5 xULN at screening Visit 1 or screening Visit 2
3. ALT and/or AST > 3.0 xULN at screening Visit 1 or screening Visit 2
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
or screening Visit 2
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: 100000004851

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-

Trade Name: Exjade
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-

Trade Name: Exjade
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-

Trade Name: Exjade
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)

Secondary Objective: Core phase
1. to evaluate both formulations on serum ferritin and compliance in ICT
naive patients after 48 weeks of treatment
2. To evaluate both formulations on change in serum ferritin after 24
weeks and 48 weeks of treatment in ICT naïve and pre-treated patients
3. To evaluate both formulations on patient satisfaction and palatability
using Patient / Observer Reported Outcomes
(PRO/ObsRO) questionnaires
4. To evaluate both formulations on overall safety
5. To evaluate compliance using a daily PRO/ObsRO questionnaire
6. To evaluate pre-dose PK data to support the assessment of
compliance
7. 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

Main Objective: 1. To evaluate both formulations on patient compliance, using stick
pack/tablet count over 24 weeks of treatment in ICT naive patients
during core phase
2. To evaluate the change from baseline in serum ferritin after 24 weeks
of treatment for both formulations in ICT naive patients during the core
phase

Primary end point(s): 1. Compliance measured by stick pack/tablet count over 24 weeks of
treatment (i.e. assessed at Week 25 visit)
2. Change from baseline in serum ferritin after 24 weeks of treatment
(i.e. serum ferritine at Week 25 visit

Timepoint(s) of evaluation of this end point: 1. 24 weeks (at Week 25 visit)
2. baseline and 24 weeks (at Week 25 visit)

Secondary Outcome(s)

Secondary end point(s): Core phase:
1. Compliance measured by stick pack/tablet count after 48 weeks of
treatment
2. Change from baseline in serum ferritin after 48 weeks of treatment
3. Change from baseline in serum ferritin after 24 weeks (i.e. assessed
at week 25 visit) and 48 weeks of treatment
4. Domain scores of treatment satisfaction and palatability over time
5. Frequency of Adverse Events (AEs) as a measure of overall safety
6. Severity of Adverse Events (AEs) as a measure of overall safety
7. Rate of dosing instructions deviations
8. Pre-dose deferasirox concentrations in all patients [except Egypt]
9. 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. 24 weeks and 48 weeks
4. Baseline and 48 weeks
5. Baseline and 48 weeks
6. Baseline and 48 weeks
7. Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45
8. Week 5 and 9

Extension phase:
Week 309

Secondary ID(s)

2013-004739-55-BE

CICL670F2202

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 15/10/2015
Contact: