Back to resultsStudy to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload
Primary Purpose
Transfusion-dependent Anemia
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Deferasirox granule formulation
Deferasirox DT formulation
Sponsored by
About this trial
This is an interventional treatment trial for Transfusion-dependent Anemia focused on measuring New formulation, deferasirox, chelation, iron overload, compliance, satisfaction, palatability, PRO, PK, safety, PK/PD, ICL670
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 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.
- (Criterion no longer applicable, removed as part of Amendment 1): Prior iron chelation therapy.
- 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).
Other protocol-defined Inclusion/Exclusion may apply.
Sites / Locations
- Children's Hospital Oakland Onc Dept
- Childrens Healthcare of Atlanta Onc Dept
- Northwestern University Onc Dept
- Children's Hospital at Montefiore
- Weill Cornell Medical College SC -
- Childrens Hospital of Philadelphia Onc. Dept
- Medical University of South Carolina Medical Uni of South Carolina
- St. Jude Children's Research Hospital Memphis St Jude
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm 1
Arm 2
Arm Description
Outcomes
Primary Outcome Measures
Compliance (using stick/pack tablet count).
Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
Change in serum ferritin in ICT naive patients.
The comparison of means between the two treatment arms of change from baseline to week 24 of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
Secondary Outcome Measures
Compliance (using stick/pack tablet count)
Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
Change in serum ferritin in ICT naive patients
The comparison of means between the two treatment arms of change from baseline to week 24 and to 48 weeks of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
Domain scores of treatment satisfaction and palatability over time
To evaluate both formulations on patient satisfaction and palatability using Patient / Observer Reported Outcomes (PRO/ObsRO) questionnaires
Overall safety, as measured by frequency and severity of adverse
This includes 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, cardiac, and growth and development evaluations will be assessed.
Rate of dosing instructions deviations ('Compliance', using a questionnaire)
This includes doses missed/not taken at the same time every day, to evaluate the compliance using a daily PRO/ObsRO questionnaire.
Pre-dose deferasirox concentrations in all patients
The pre-dose concentration by incident dose will be plotted for Week 1, Week 3, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29, Week 33, Week, 37, Week 41 and Week 45 based on data from all patients. Pre-dose PK data from all patients will be analyzed to support the assessment of compliance.Predicted individual concentrations derived from the compartmental model will be compared to respective observed pre-dose concentrations. Distributions of the difference between predicted and observed values will be shown graphically by boxplots for both treatment groups and visit.
Post-dose deferasirox concentrations between 2 and 4 hours post-dose at Weeks 5 and 9
post-dose PK data to be analyzed along with pre-dose PK data
PK/PD relationship
To explore exposure-response relationships for measures of safety and effectiveness: serum creatinine change from baseline, notable serum creatinine values, serum creatinine clearance change from baseline and notable serum creatinine clearance categories, serum ferritin change from baseline, in relationship to derived PK parameters for pre- and post-dose deferasirox concentrations.
Assess additional safety, as measured by frequency and severity of adverse for granules during extension phase
This includesactive 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02435212
Brief 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
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 21, 2015 (Actual)
Primary Completion Date
May 31, 2018 (Actual)
Study Completion Date
December 15, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transfusion-dependent Anemia
Keywords
New formulation, deferasirox, chelation, iron overload, compliance, satisfaction, palatability, PRO, PK, safety, PK/PD, ICL670
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
224 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Active Comparator
Arm Title
Arm 2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Deferasirox granule formulation
Other Intervention Name(s)
ICL670
Intervention Description
Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use.
Intervention Type
Drug
Intervention Name(s)
Deferasirox DT formulation
Other Intervention Name(s)
ICL670
Intervention Description
Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use
Primary Outcome Measure Information:
Title
Compliance (using stick/pack tablet count).
Description
Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
Time Frame
24 weeks
Title
Change in serum ferritin in ICT naive patients.
Description
The comparison of means between the two treatment arms of change from baseline to week 24 of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
Time Frame
Baseline, 24 weeks
Secondary Outcome Measure Information:
Title
Compliance (using stick/pack tablet count)
Description
Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
Time Frame
48 weeks
Title
Change in serum ferritin in ICT naive patients
Description
The comparison of means between the two treatment arms of change from baseline to week 24 and to 48 weeks of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
Time Frame
Baseline, 24 weeks, 48 weeks
Title
Domain scores of treatment satisfaction and palatability over time
Description
To evaluate both formulations on patient satisfaction and palatability using Patient / Observer Reported Outcomes (PRO/ObsRO) questionnaires
Time Frame
From baseline to 48 weeks
Title
Overall safety, as measured by frequency and severity of adverse
Description
This includes 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, cardiac, and growth and development evaluations will be assessed.
Time Frame
From Baseline to 48 weeks
Title
Rate of dosing instructions deviations ('Compliance', using a questionnaire)
Description
This includes doses missed/not taken at the same time every day, to evaluate the compliance using a daily PRO/ObsRO questionnaire.
Time Frame
From Baseline to 48 weeks
Title
Pre-dose deferasirox concentrations in all patients
Description
The pre-dose concentration by incident dose will be plotted for Week 1, Week 3, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29, Week 33, Week, 37, Week 41 and Week 45 based on data from all patients. Pre-dose PK data from all patients will be analyzed to support the assessment of compliance.Predicted individual concentrations derived from the compartmental model will be compared to respective observed pre-dose concentrations. Distributions of the difference between predicted and observed values will be shown graphically by boxplots for both treatment groups and visit.
Time Frame
at Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45 (13 samples)
Title
Post-dose deferasirox concentrations between 2 and 4 hours post-dose at Weeks 5 and 9
Description
post-dose PK data to be analyzed along with pre-dose PK data
Time Frame
Week 5, Week 9
Title
PK/PD relationship
Description
To explore exposure-response relationships for measures of safety and effectiveness: serum creatinine change from baseline, notable serum creatinine values, serum creatinine clearance change from baseline and notable serum creatinine clearance categories, serum ferritin change from baseline, in relationship to derived PK parameters for pre- and post-dose deferasirox concentrations.
Time Frame
From Baseline to 48 weeks
Title
Assess additional safety, as measured by frequency and severity of adverse for granules during extension phase
Description
This includesactive 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.
Time Frame
From Baseline to 305 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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 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.
(Criterion no longer applicable, removed as part of Amendment 1): Prior iron chelation therapy.
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).
Other protocol-defined Inclusion/Exclusion may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Oakland Onc Dept
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Childrens Healthcare of Atlanta Onc Dept
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Northwestern University Onc Dept
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Weill Cornell Medical College SC -
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Childrens Hospital of Philadelphia Onc. Dept
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104 4399
Country
United States
Facility Name
Medical University of South Carolina Medical Uni of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
St. Jude Children's Research Hospital Memphis St Jude
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Novartis Investigative Site
City
Edegem
State/Province
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Brussel
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Alexandria
ZIP/Postal Code
21131
Country
Egypt
Facility Name
Novartis Investigative Site
City
Creteil
ZIP/Postal Code
94000
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700017
Country
India
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16128
Country
Italy
Facility Name
Novartis Investigative Site
City
Palermo
State/Province
PA
ZIP/Postal Code
90127
Country
Italy
Facility Name
Novartis Investigative Site
City
Palermo
State/Province
PA
ZIP/Postal Code
90146
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80132
Country
Italy
Facility Name
Novartis Investigative Site
City
Hazmiyeh
State/Province
Beirut
ZIP/Postal Code
PO BOX 213
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Ipoh
State/Province
Perak
ZIP/Postal Code
30450
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Kuala Lumpur
ZIP/Postal Code
50589
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Muscat
ZIP/Postal Code
123
Country
Oman
Facility Name
Novartis Investigative Site
City
Panama City
State/Province
Republica De Panama
ZIP/Postal Code
0801
Country
Panama
Facility Name
Novartis Investigative Site
City
Quezon City
ZIP/Postal Code
1100
Country
Philippines
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
117198
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Bangkok noi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Muang
State/Province
Chiangmai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Novartis Investigative Site
City
Tunis
ZIP/Postal Code
1006
Country
Tunisia
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload
We'll reach out to this number within 24 hrs