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

NCT02435212 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CICL670F22022013-004739-55
• Study Type: interventional
• Target: 224
• Locations: 16 countries
• Sites: 42

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

Keywords

New formulation; deferasirox; chelation; iron overload; compliance; satisfaction; palatability; PRO; PK; safety; PK/PD; ICL670

Outcome Measures

Primary Outcomes (2)

• Percentage of Overall Compliance Using Stick Pack or Tablet Counts in Iron Chelation Therapy (ICT)-naïve Participants During the Core Phase

  Compliance was calculated as the ratio of total count consumed to total count prescribed of deferasirox granule stick packs or dispersible tablets, where total count consumed was derived from cumulative dispensed, returned and lost/wasted counts over 24 weeks of treatment and total count prescribed was derived from cumulative prescribed count over 24 weeks of treatment.

  24 weeks

• Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase

  The analysis included the comparison of means between the two treatment arms of change from baseline after 24 weeks of treatment in serum ferritin in pediatric ICT naïve participants with iron overload. The endpoint was assessed at Week 25 visit.

  From Baseline to Week 25

Secondary Outcomes (15)

• Percentage of Overall Compliance Using Stick Pack or Tablet Counts in ICT-naïve Participants During the Core Phase

  48 weeks

• Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in ICT naïve Participants During the Core Phase

  From Baseline to 48 weeks

• Change From Baseline in Serum Ferritin (SF) for Both Study Drug Formulations in Pre-treated Participants During the Core Phase

  From Baseline to Week 25 and Week 48

• Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Patient Reported Outcomes (PRO) Questionnaires

  At Week 2, Week 3, Week 25 and Week 48

• Change Over-time in Domain Score of Modified Satisfaction With Iron Chelation Therapy (mSICT) Using Observer Reported Outcomes (ObsRO) Questionnaire (Caregiver's Perspective)

  At Week 2, Week 3, Week 25 and Week 48

Other Outcomes (1)

• Exposure-Response Relationship in Relation to Pre- and Post-Dose Deferasirox Concentrations (PK/PD Relationship)

  From Baseline to 48 weeks

Study Arms (2)

DFX DT

ACTIVE COMPARATOR

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

Drug: Deferasirox DT formulation

DFX Granule

EXPERIMENTAL

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

Drug: Deferasirox granule formulation

Interventions

Deferasirox granule formulation 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.

Also known as: ICL670

DFX Granule

Deferasirox DT formulation 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.

Also known as: ICL670

DFX DT

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (43)

Novartis Investigative Site

Oakland, California, 94609-1809, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30342, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60611, United States

Location

Novartis Investigative Site

New York, New York, 10021, United States

Location

Weill Cornell Medical College SC -

New York, New York, 10021, United States

Location

Childrens Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Novartis Investigative Site

The Bronx, New York, 10467, United States

Location

Childrens Hospital of Philadelphia Onc. Dept

Philadelphia, Pennsylvania, 19104 4399, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104 4399, United States

Location

Medical Uni of South Carolina Medical Uni of South Carolina

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Memphis, Tennessee, 38105, United States

Location

St. Jude Children's Research Hospital Memphis St Jude

Memphis, Tennessee, 38105, United States

Location

Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Plovdiv, 4002, Bulgaria

Location

Novartis Investigative Site

Sofia, 1527, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Alexandria, 21131, Egypt

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Kolkata, West Bengal, 700017, India

Location

Novartis Investigative Site

Genova, GE, 16128, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Palermo, PA, 90146, Italy

Location

Novartis Investigative Site

Napoli, 80132, Italy

Location

Novartis Investigative Site

Hazmiyeh, Beyrouth, PO BOX 213, Lebanon

Location

Novartis Investigative Site

Ipoh, Perak, 30450, Malaysia

Location

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

Location

Novartis Investigative Site

Kuala Lumpur, 50589, Malaysia

Location

Novartis Investigative Site

Pulau Pinang, 10990, Malaysia

Location

Novartis Investigative Site

Muscat, 123, Oman

Location

Novartis Investigative Site

Panama City, Republica de Panama, 0801, Panama

Location

Novartis Investigative Site

Quezon, 1100, Philippines

Location

Novartis Investigative Site

Quezon City, 1100, Philippines

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Bangkok Noi, Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Muang, Chiangmai, 50200, Thailand

Location

Novartis Investigative Site

Tunis, 1006, Tunisia

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Iron Overload; Patient Compliance; Personal Satisfaction

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: May 6, 2015
• Study Start: October 21, 2015
• Primary Completion: May 31, 2018
• Study Completion: January 15, 2024
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); PH (2); TU (3); HU (1); US (13); IT (4); EG (1); FR (2); IN (1); BU (3); PA (1); LE (1); MY (4); RU (1); TH (2); OM (1)