Additional identifiers
EudraCT number
2004-000597-31
ClinicalTrials.gov number
NCT01090323
Protocol/serial number
CICL670 0109
Study information
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
Acronym
ICL109
Study hypothesis
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
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.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Deferasirox (ICL670), deferoxamine (DFO)
Primary outcome measures
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
Secondary outcome measures
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
Overall trial start date
01/01/2004
Overall trial end date
01/01/2006
Reason abandoned
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
195
Participant 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
Recruitment start date
01/01/2004
Recruitment end date
01/01/2006
Locations
Countries of recruitment
Canada, France, Italy, United Kingdom, United States of America
Trial participating centre
Children's Hospital & Research Center at Oakland
Oakland
94609-1809
United States of America
Sponsor information
Organisation
Novartis Pharmaceuticals Corporation (USA)
Sponsor details
One Health Plaza
East Hanover
07936
United States of America
+1 (0)862 778 2791
halyna.wysowskyj@pharma.novartis.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Novartis Pharmaceuticals Corporation
Alternative name(s)
NPC
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
See https://clinicaltrials.gov/ct2/show/results/NCT01090323
Publication summary
2007 results in: http://www.ncbi.nlm.nih.gov/pubmed/17233848
Publication citations
-
Results
Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, Files B, Hassell K, Kelly P, Wilson F, Bernaudin F, Forni GL, Okpala I, Ressayre-Djaffer C, Alberti D, Holland J, Marks P, Fung E, Fischer R, Mueller BU, Coates T, , A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease., Br. J. Haematol., 2007, 136, 3, 501-508, doi: 10.1111/j.1365-2141.2006.06455.x.