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

NCT ID: NCT02435212

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-21
• Study Completion Date: 2024-01-15

Brief Summary

This was 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 dispersible tablet (DT) formulation in children and adolescents aged ≥ 2 and < 18 years at enrolment with any transfusion-dependent anemia requiring chelation therapy due to iron overload, to demonstrate the effect of improved compliance on iron burden.

Randomization was stratified by age groups (2 to <10 years, 10 to <18 years) and prior iron chelation therapy (Yes/ No). There were two study phases which include a 1 year core phase where participants were randomized to a 48 week treatment period to either Deferasirox DT or granules, and an optional extension phase where all participants received the granules up to 5 years. Participants who demonstrated benefit to granules or DT in the core phase, and/or expressed the wish to continue in the optional extension phase on granules, were offered this possibility until there was local access to the new formulation (granules or film-coated tablet (FCT)) or up to 5 years, whichever occurred first.

Conditions

Transfusion-dependent Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DFX DT

Participants will be administered deferasirox dispersible tablets orally once daily based on body weight for 48 weeks.

Group Type: ACTIVE_COMPARATOR

Deferasirox DT formulation

Intervention Type: DRUG

Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use and will be administered based on body weight.

DFX Granule

Participants will be administered deferasirox granules orally once daily in the form of stick packs based on body weight for 48 weeks.

Group Type: EXPERIMENTAL

Deferasirox granule formulation

Intervention Type: DRUG

Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use and will be administered based on body weight.

Interventions

Deferasirox granule formulation

Deferasirox granules will be provided as stick packs containing 90 mg, 180 mg and 360 mg granules for oral use and will be administered based on body weight.

Intervention Type: DRUG

Deferasirox DT formulation

Deferasirox DT will be provided as 125 mg, 250 mg and 500 mg dispersible tablets for oral use and will be administered based on body weight.

Intervention Type: DRUG

Other Intervention Names

ICL670; 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..
• 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).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Oakland, California, United States

Novartis Investigative Site

Atlanta, Georgia, United States

Novartis Investigative Site

Chicago, Illinois, United States

Novartis Investigative Site

New York, New York, United States

Weill Cornell Medical College SC -

New York, New York, United States

Childrens Hospital at Montefiore

The Bronx, New York, United States

Novartis Investigative Site

The Bronx, New York, United States

Childrens Hospital of Philadelphia Onc. Dept

Philadelphia, Pennsylvania, United States

Novartis Investigative Site

Philadelphia, Pennsylvania, United States

Medical Uni of South Carolina Medical Uni of South Carolina

Charleston, South Carolina, United States

Novartis Investigative Site

Charleston, South Carolina, United States

Novartis Investigative Site

Memphis, Tennessee, United States

St. Jude Children's Research Hospital Memphis St Jude

Memphis, Tennessee, United States

Novartis Investigative Site

Edegem, Antwerpen, Belgium

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Varna, , Bulgaria

Novartis Investigative Site

Alexandria, , Egypt

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Kolkata, West Bengal, India

Novartis Investigative Site

Genova, GE, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Palermo, PA, Italy

Novartis Investigative Site

Napoli, , Italy

Novartis Investigative Site

Hazmiyeh, Beyrouth, Lebanon

Novartis Investigative Site

Ipoh, Perak, Malaysia

Novartis Investigative Site

Kuching, Sarawak, Malaysia

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Novartis Investigative Site

Pulau Pinang, , Malaysia

Novartis Investigative Site

Muscat, , Oman

Novartis Investigative Site

Panama City, Republica de Panama, Panama

Novartis Investigative Site

Quezon, , Philippines

Novartis Investigative Site

Quezon City, , Philippines

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Bangkok Noi, Bangkok, Thailand

Novartis Investigative Site

Muang, Chiangmai, Thailand

Novartis Investigative Site

Tunis, , Tunisia

Novartis Investigative Site

Adana, , Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Countries

United States; Belgium; Bulgaria; Egypt; France; Hungary; India; Italy; Lebanon; Malaysia; Oman; Panama; Philippines; Russia; Thailand; Tunisia; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-004739-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CICL670F2202

Identifier Type: -

Identifier Source: org_study_id