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: 9 January 2017
• Main ID: EUCTR2013-004739-55-DK
• Date of registration: 04/08/2016
• 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: 13/09/2016
• 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: Single blind: no Double blind: no Parallel group: Cross over: no Other: no 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, Italy, Lebanon, Malaysia, Oman, Panama, Philippines, Russian Federation, Thailand, Tunisia, Turkey, United Arab Emirates, United States

Contacts

• Name: Medical Information
• Affiliation: Novartis Healthcare A/S

• Name: Medical Information
• Affiliation: Novartis Healthcare A/S

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 assent of patients according to local guidelines.
2. Male and female children and adolescents aged = 2 and < 18 years.
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).
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. Creatinine clearance will be estimated from serum creatinine (using the Schwartz formula) at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria.
2. Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
3. ALT and/or AST > 3.0 x ULN.
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 non-first void 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

transfusion-dependent anemia requiring chelation therapy due to iron overload
MedDRA version: 19.0 Level: LLT Classification code 10074295 Term: Transfusion dependent anemia System Organ Class: 100000004851

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

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)

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

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

Secondary Objective: 1.to evaluate both formulations on serum ferritin in ICT naive and pre-treated 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

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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 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

Secondary end point(s): 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
6. Post-dose deferasirox concentrations between 2 and 4 hours post-dose at Weeks 5 and 9 (2 samples)

Secondary ID(s)

CICL670F2202

2013-004739-55-BE

Source(s) of Monetary Support

Novartis Pharma Services AG