Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).

Sickle Cell Disease Clinical Trial

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01090323
• Other study ID #: CICL670A0109E1
• Secondary ID: EudraCT no. 2004
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2010
• Last updated: May 3, 2011
• Start date: July 2004

Study information

• Verified date: May 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationItaly: Ministry of HealthCanada: Health CanadaFrance: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santéUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Other known NCT identifiers

• NCT00171197

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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 ß-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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• ICL670
Daily doses of ICL670 were taken orally 30 minutes before breakfast. The doses range from 5-40 mg/kg and were determined based on the patient's trend in serum ferritin over time during the core study (0109) and on the frequency of blood transfusions the patient received. The treatment duration was up to 4 years.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Paris
Italy	Novartis Investigative Site	Catania
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Roma
United Kingdom	Novartis Investigative Site	London
United States	Grady Hospital, Georgia Comprehensive Sickle Cell Center	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	University of Colorado Health Science Center	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Children's Hospital	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	St. Jude's Children Research Hospital	Memphis	Tennessee
United States	University of South Alabama College of Medicine	Mobile	Alabama
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	New York Presbyterian Hospital	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Children's Hospital & Research Center at Oakland	Oakland	California
United States	Yasin	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	LSUHSC Dept of Pediatrics	Shreveport	Louisiana
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	St Joseph Children's Hospital of Tampa	Tampa	Florida
United States	Scott & White Memorial Hospital	Temple	Texas
United States	Howard University Hospital	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events After Start of ICL670	Safety as assessed by the number of participants with adverse event or death after the start of ICL670.	0 - 60 months	Yes
Secondary	Change in Serum Ferritin From Start of ICL670 to End of Study	The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670.	0 - 60 months	No