A randomised, multicentre, open label, phase Il study to evaluate the safety, tolerability, pharmacokinetics and the effects on liver iron concentration of repeated doses of 10 mg/kg/day of ICL670 relative to deferoxamine in sickle cell disease (SCD) patients with transfusional haemosiderosis

ISRCTN	ISRCTN05896089
DOI	https://doi.org/10.1186/ISRCTN05896089
ClinicalTrials.gov (NCT)	NCT01090323
Clinical Trials Information System (CTIS)	2004-000597-31
Protocol serial number	CICL670 0109
Sponsor	Novartis Pharmaceuticals Corporation (USA)
Funder	Novartis Pharmaceuticals Corporation

Submission date: 23/07/2003
Registration date: 05/09/2003
Last edited: 21/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Elliot Vichinsky
Scientific

Children's Hospital & Research Center at Oakland
747 52nd Street
OPC-PCRC, 1st Floor
Oakland
94609-1809
United States of America

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised, multicentre, open label, phase Il study to evaluate the safety, tolerability, pharmacokinetics and the effects on liver iron concentration of repeated doses of 10 mg/kg/day of ICL670 relative to deferoxamine in sickle cell disease (SCD) patients with transfusional haemosiderosis
Study acronym	ICL109
Study objectives	The primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine.
Ethics approval(s)	The trial was conducted in accordance with the Declaration of Helsinki. Institutional Review Board approval was obtained at each participating institution and written informed consent was obtained from all patients or guardians prior to participation in any study procedures.
Health condition(s) or problem(s) studied	Sickle cell disease (SCD)
Intervention	The study duration was 52 weeks. The initial 24 patients enroled were randomised to receive deferasirox 10 mg/kg or deferoxamine at recommended doses of 20 - 60 mg/kg based on initial liver iron concentration (LIC). Subsequently, additional safety information became available for deferasirox suggesting a need to modify the starting dose. Therefore, following the enrolment of the first 24 patients, the study was amended so that all subsequent patients randomised to deferasirox were dosed at 10 - 30 mg/kg according to baseline LIC. Deferasirox was given once daily each morning as a dispersed solution in water, half-an-hour before breakfast. Deferoxamine was administered as a slow subcutaneous infusion over 8 - 12 hours using electronic Microject Chrono® (Medical Technology, Turin, Italy) infusion pumps on 5 - 7 days a week.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Deferasirox (ICL670), deferoxamine (DFO)
Primary outcome measure(s)	Safety assessments: 1. Laboratory assessments: performed monthly and included complete blood counts with differential counts: 1.1. Biochemistry testing (electrolytes, glucose, liver function tests, gamma-glutaryl-transferase, lactate dehydrogenase, cholesterol, triglycerides, uric acid, total protein, C-reactive protein, copper and zinc level) 1.2. Iron parameters (total iron, transferrin, transferrin saturation and ferritin) 1.3. Urinary testing performed on random collections (determination of creatinine, total protein and albumin) 2. Physical examinations (electrocardiograms [ECG], audiometry and ophthalmological tests) were performed at baseline, 12, 24, 36 and 52 weeks 3. In patients less than 16 years of age, additional assessments included growth velocity and pubertal stage
Key secondary outcome measure(s)	Efficacy assessments: 1. Liver iron concentration: determined by superconducting quantum interference device (SQUID) biosusceptometry at baseline, 24 and 52 weeks 2. Serum ferritin: assessed monthly during the study and the change was determined using the baseline and final ferritin level Compliance: 1. For deferasirox, compliance was assessed by counting the number of tablets returned in bottles at each visit 2. For deferoxamine, the numbers of vials returned at each visit were counted
Completion date	01/01/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	195
Key inclusion criteria	Patients with SCD requiring chronic blood transfusions to prevent complications (stroke, chest syndrome) and thus developing transfusional iron overload requiring chronic chelation therapy.
Key exclusion criteria	1. Serum creatinine above the upper limit of normal (ULN) 2. Significant proteinuria (as indicated by a urinary protein:creatinine ratio of greater than or equal to 0.5 confirmed at two visits) 3. Active hepatitis B or C: 3.1. Active hepatitis B defined as liver function tests above the normal range, together with a positive antigen (hepatitis B e antigen, hepatitis B surface antigen) test or positive immunoglobulin M (IgM) core antibody test in conjunction with a negative hepatitis B surface antibody test 3.2. Active hepatitis C defined as liver function tests above the normal range in the presence of a positive hepatitis C antibody test and detectable hepatitis C ribonucleic acid (RNA) levels 4. Second and third atrioventricular block 5. QT interval prolongation 6. Therapy with digoxin or similar medications (treatment with β-blockers or angiotensin-converting enzyme inhibitors was permitted) 7. Chelation therapy-associated ocular toxicity
Date of first enrolment	01/01/2004
Date of final enrolment	01/01/2006

Locations

Countries of recruitment

United Kingdom
Canada
France
Italy
United States of America

Study participating centre

Children's Hospital & Research Center at Oakland

Oakland
94609-1809
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2007		Yes	No
Basic results				No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

21/03/2016: added link to results - basic reporting.