Clinical trial NCT01090323: Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
Official title: A One Year Open Label, Non-comparative Extension to a Randomized, Multicenter, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration (LIC) of Repeated Doses of 5-30mg/kg/Day ICL670 Relative to Deferoxamine (DFO) in Sickle Cell Disease (SCD) Patients With Transfusional Hemosideresis (THS) [Amendment 3: Extension Prolonged to 4-years]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Deferasirox
ICL670A
Iron chelators
Sickle Cell Disease
Transfusional Hemosiderosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-03-19
Enrollment: 185
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The safety, tolerability, effects on liver iron concentration and pharmacokinetics of ICL670 is studied in sickle cell disease patients with transfusional hemosiderosis.

Detailed description: The treatment period started once the patient completed the core study and signed informed consent. It is continued for up to 4 years. Safety parameters were assessed every 4 weeks. Eye and Ear examinations were performed on a yearly basis. To further investigate the extent of iron overload, serum ferritin, iron, and transferrin were monitored every four weeks. The Program Safety Board monitored the safety of ICL670 during the study to evaluate and categorize any serious case reported in association with ICL670.

Eligibility criteria: Inclusion Criteria:

Patients were included who met the following criteria:

* Completion of the core \[Study 0109\]
* Serum ferritin greater than or equal to 500 µg/L
* Ability to comply with all study-related procedures, medications, and evaluations
* Sexually active post-menarche female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
* Written informed consent and assent by the patient and or their parents or legal guardian.

Additional inclusion criteria for pediatric patients The definition of the term 'pediatric' for enrollment and study conduct was in accordance with local law. Parents or the legal guardians were fully informed by the investigator as to the requirements of the study. The pediatric patients themselves were informed according to their capabilities in a language and terms that they were able to understand. Written informed consent was obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients had to also personally sign their written informed consent.

Exclusion Criteria:

Patients who met the following criteria were to be excluded:

* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* Serum creatinine above the age-appropriate upper limit of normal within one week prior to entry
* Patients with ALT ≥ 500 U/L within one week prior to entry
* Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline
* Pregnancy (as indicated by serum β-HCG pregnancy test for all female patients with the potential to become pregnant) and patients who are breastfeeding
* Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Participants With Adverse Events After Start of ICL670
timeFrame: 0 - 60 months
Secondary outcomes:
measure: Change in Serum Ferritin From Start of ICL670 to End of Study
timeFrame: 0 - 60 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama College of Medicine
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center at Oakland
state: California
city: Denver
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: St Joseph Children's Hospital of Tampa
state: Florida
city: Atlanta
country: United States
facility: Grady Hospital, Georgia Comprehensive Sickle Cell Center
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Shreveport
country: United States
facility: LSUHSC Dept of Pediatrics
state: Louisiana
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Yasin
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Sumter
country: United States
facility: Santee Hematology/Oncology
state: South Carolina
city: Memphis
country: United States
facility: St. Jude's Children Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Toronto
country: Canada
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Catania
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: