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

March 26, 2024 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
224

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussel, Belgium, 1200
        • Novartis Investigative Site
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Novartis Investigative Site
  • Bulgaria
      • Plovdiv, Bulgaria, 4002
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1527
        • Novartis Investigative Site
      • Varna, Bulgaria, 9010
        • Novartis Investigative Site
  • Egypt
      • Alexandria, Egypt, 21131
        • Novartis Investigative Site
  • France
      • Creteil, France, 94000
        • Novartis Investigative Site
      • Paris 15, France, 75015
        • Novartis Investigative Site
  • Hungary
      • Debrecen, Hungary, 4032
        • Novartis Investigative Site
  • India
    • West Bengal
      • Kolkata, West Bengal, India, 700017
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80132
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16128
        • Novartis Investigative Site
    • PA
      • Palermo, PA, Italy, 90127
        • Novartis Investigative Site
      • Palermo, PA, Italy, 90146
        • Novartis Investigative Site
  • Lebanon
    • Beirut
      • Hazmiyeh, Beirut, Lebanon, PO BOX 213
        • Novartis Investigative Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 50589
        • Novartis Investigative Site
      • Pulau Pinang, Malaysia, 10990
        • Novartis Investigative Site
    • Perak
      • Ipoh, Perak, Malaysia, 30450
        • Novartis Investigative Site
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Novartis Investigative Site
  • Oman
      • Muscat, Oman, 123
        • Novartis Investigative Site
  • Panama
    • Republica De Panama
      • Panama City, Republica De Panama, Panama, 0801
        • Novartis Investigative Site
  • Philippines
      • Quezon City, Philippines, 1100
        • Novartis Investigative Site
  • Russian Federation
      • Moscow, Russian Federation, 117198
        • Novartis Investigative Site
  • Thailand
    • Bangkok
      • Bangkok noi, Bangkok, Thailand, 10700
        • Novartis Investigative Site
    • Chiangmai
      • Muang, Chiangmai, Thailand, 50200
        • Novartis Investigative Site
  • Tunisia
      • Tunis, Tunisia, 1006
        • Novartis Investigative Site
  • Turkey
      • Adana, Turkey, 01330
        • Novartis Investigative Site
      • Ankara, Turkey, 06100
        • Novartis Investigative Site
      • Izmir, Turkey, 35040
        • Novartis Investigative Site
  • United States
    • California
      • Oakland, California, United States, 94609-1809
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Novartis Investigative Site
    • New York
      • Bronx, New York, United States, 10467
        • Childrens Hospital at Montefiore
      • New York, New York, United States, 10021
        • Weill Cornell Medical College SC -
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104 4399
        • Childrens Hospital of Philadelphia Onc. Dept
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical Uni of South Carolina Medical Uni Of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital Memphis St Jude

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 13 years (Child)

Accepts Healthy Volunteers

No

Description

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..
  • 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).
  • Direct (conjugated) bilirubin >2 x ULN at screening visit 1 or screening visit 2.
  • Local access to new formulation (granules or FCT) is available (For optional extension phase eligibility only).

Other protocol-defined Inclusion/Exclusion may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • ICL670
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 Names:
  • ICL670

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Compliance (using stick/pack tablet count).
Time Frame: 24 weeks
Evaluate patient compliance measured by stick pack/tablet count in ICT naïve patients during core phase.
24 weeks
Change in serum ferritin in ICT naive patients.
Time Frame: From Baseline to 24 weeks
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.
From Baseline to 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
48 weeks
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
From baseline to 48 weeks
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.
From Baseline to 48 weeks
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.
From Baseline to 48 weeks
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.
at Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, and 45 (13 samples)
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
Week 5, Week 9
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.
From Baseline to 48 weeks
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.
From Baseline to 305 weeks
Change in serum ferritin in ICT naive patients
Time Frame: From Baseline to 48 weeks
The comparison of means between the two treatment arms of change from baseline to week 48 week of treatment in serum ferritin in pediatric ICT naïve patients with iron overload.
From Baseline to 48 weeks
Change in serum ferritin in pre-treated patients
Time Frame: From Baseline to 24 weeks and 48 weeks
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 pre-treated patients.
From Baseline to 24 weeks and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 21, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 6, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CICL670F2202
  • 2013-004739-55 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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