Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis

NCT03372083 | Completed Phase 4 Results

• 2 other identifiers: CICL670F24292016-003482-25
• Study Type: interventional
• Target: 44
• Locations: 7 countries
• Sites: 10

Brief Summary

This study employed a prospective, single-arm, global multi-center interventional open-label, non-randomized design to identify and assess safety profile of the crushed deferasirox FCT when administered up to 24 weeks in pediatric patients aged ≥2 to \<6 years with transfusional hemosiderosis. The study was designed to enroll a minimum of 40 patients. Forty-four patients were treated and analyzed.

Conditions

Iron Overload

Keywords

Iron Chelation Therapy; Deferasirox; Asunra; Jadenu; Exjade; ICL 670; Pediatric

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Selected Gastrointestinal Disorders up to 24 Weeks

  To assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal (GI) disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea, and vomiting). Only descriptive analysis performed.

  Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Secondary Outcomes (28)

• Adverse Events Profile

  Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

• Number of Participants With Notable Changes in ECG Values From Baseline

  Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

• Absolute Change From Baseline in Serum Ferritin (SF)

  Baseline (BL), Week 4, Week 8, Week 12, Week 16, EOT (Week 24)

• Number of Participants With Worst Post-baseline Values in Selected Chemistry Parameters

  Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

• Number of Participants With Clinically Significant Auditory Assessments Changes From Baseline

  Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Study Arms (1)

Deferasirox

EXPERIMENTAL

Crushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing was based on subject's weight.

Drug: Deferasirox

Interventions

Deferasirox DRUG

Deferosirox was provided in tablet forms of 90, 180 and 360mg. Tablets were crushed in the home environment and administered by sprinkling the full dose on to soft food to be consumed immediately.

Also known as: ICL670

Deferasirox

Eligibility Criteria

• Age: 2 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients ≥2 to \<6 years old diagnosed with transfusional hemosiderosis
• Documented history of red blood cell transfusions
• Written informed consent/assent before any study-specific procedures. The consent will be obtained from caregiver(s) or patient's legal representative. Investigators will also obtain assent of patients according to local, regional, or national regulations.
• For patients on prior DFX: Serum ferritin (SF) \>500 ng/mL, measured at screening visit 1 and requiring a DFX daily dose equivalent to FCT ≥ 7mg/kg/day.
• For patients on a prior chelator other than DFX (e.g. deferiprone or deferoxamine) or chelation naive: Serum ferritin (SF) \>1000 ng/mL measured at screening visits 1 and 2.

You may not qualify if:

• Patients that receive more than one iron chelator at the same time as current iron chelation treatment. (Patients who have received combination therapy in their medical history but are currently being treated with a single ICT agent are eligible.)
• Patients continuing on deferoxamine or deferiprone in addition to study treatment. (Patients switching to or continuing on deferasirox are eligible).
• Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
• Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 mg/mg in a non-first void sample urine measured at screening visit 1.
• Serum creatinine \> age adjusted ULN measured at any screening visit
• Creatinine clearance below 90 mL/minute measured at any screening visit. Creatinine clearance using the Schwartz formula will be estimated from serum creatinine measured at each respective visit.
• ALT and/or AST \> 2.5 x ULN measured at screening visit 1.
• Total bilirubin (TBIL) \>1.5 x ULN measured at screening visit 1.
• Patients with significant impaired GI function or GI disease that may significantly alter the absorption of oral deferasirox FCT (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• History of and/or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive.
• Liver disease with severity of Child-Pugh Class B or C.
• History of hypersensitivity to any of the study drug or excipients.
• Patients participating in another clinical trial or receiving an investigational drug.
• Patients with a known history of HIV seropositivity.
• Patients unwilling or unable to comply with the protocol.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Zagazig, 44519, Egypt

Location

Novartis Investigative Site

Cona, FE, 44100, Italy

Location

Novartis Investigative Site

Cagliari, ITA, 09121, Italy

Location

Novartis Investigative Site

Napoli, 80138, Italy

Location

Novartis Investigative Site

Hazmiyeh, Beyrouth, PO BOX 213, Lebanon

Location

Novartis Investigative Site

Muscat, 123, Oman

Location

Novartis Investigative Site

Bangkok Noi, Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Muang, Chiangmai, 50200, Thailand

Location

Novartis Investigative Site

Dubai, 9115, United Arab Emirates

Location

Novartis Investigative Site

London, NW1 2BU, United Kingdom

Location

MeSH Terms

Conditions

Iron Overload

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

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

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 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: December 13, 2017
• Study Start: January 16, 2018
• Primary Completion: December 5, 2019
• Study Completion: December 5, 2019
• Last Updated: August 25, 2020
• Results First Posted: August 3, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); OM (1); TH (2); AE (1); EG (1); LE (1); IT (3)