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Trial record 1 of 3 for:    f2202
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Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron Overload

This study is currently recruiting participants.
Verified July 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02435212
First Posted: May 6, 2015
Last Update Posted: July 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose

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.


Condition Intervention Phase
Transfusion-dependent Anemia Drug: Deferasirox granule formulation Drug: Deferasirox DT formulation Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Compliance (using stick/pack tablet count). [ Time Frame: 48 weeks ]
    Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.

  • Change in serum ferritin in ICT naive patients. [ Time Frame: Baseline, 48 weeks ]
    The comparison of means between the two treatment arms of change from baseline to week 48 of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.


Secondary Outcome Measures:
  • Domain scores of treatment satisfaction and palatability over time [ Time Frame: From baseline to 48 weeks ]
    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 [ Time Frame: From Baseline to 48 weeks ]
    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) [ Time Frame: From Baseline to 48 weeks ]
    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 [ Time Frame: at Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45 (13 samples) ]
    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 [ Time Frame: Week 5, Week 9 ]
    post-dose PK data to be analyzed along with pre-dose PK data

  • Change in serum ferritin in ICT naïve and pretreated patients [ Time Frame: Baseline, 48 weeks ]
    To evaluate absolute and relative change from baseline in serum ferritin in both populations.

  • PK/PD relationship [ Time Frame: From Baseline to 48 weeks ]
    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 [ Time Frame: From Baseline to 305 weeks ]
    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.


Estimated Enrollment: 240
Actual Study Start Date: October 21, 2015
Estimated Study Completion Date: March 29, 2024
Estimated Primary Completion Date: March 29, 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 Drug: Deferasirox DT formulation
Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use
Other Name: Exjade, ICL670
Experimental: Arm 2 Drug: Deferasirox granule formulation
Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use.
Other Name: ICL670

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  • 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).

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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435212


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

  Show 39 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02435212     History of Changes
Other Study ID Numbers: CICL670F2202
2013-004739-55 ( EudraCT Number )
First Submitted: March 17, 2015
First Posted: May 6, 2015
Last Update Posted: July 31, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
New formulation, deferasirox, chelation, iron overload, compliance, satisfaction, palatability, PRO, PK, safety, PK/PD, ICL670

Additional relevant MeSH terms:
Iron Overload
Anemia
Iron Metabolism Disorders
Metabolic Diseases
Hematologic Diseases
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action