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11 February 2012
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| 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 |
| ClinicalTrials.gov identifier | |
| Public 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 |
| Scientific title | |
| Acronym | ICL109 |
| Serial number at source | CICL670 0109 |
| 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. |
| Lay summary | |
| 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 |
| Countries of recruitment | Canada, France, Italy, United Kingdom, United States of America |
| Disease/condition/study domain | Sickle cell disease (SCD) |
| Participants - 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. |
| Participants - 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 |
| Anticipated start date | 01/01/2004 |
| Anticipated end date | 01/01/2006 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 195 |
| Interventions |
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. |
| 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 |
| 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 |
| Sources of funding | Novartis Pharmaceuticals Corporation (USA) |
| Trial website | |
| Publications | Results in http://www.ncbi.nlm.nih.gov/pubmed/17233848 |
| Contact name | Dr Elliot Vichinsky |
| Address |
Children's Hospital & Research Center at Oakland
747 52nd Street OPC-PCRC, 1st Floor |
| City/town | Oakland |
| Zip/Postcode | 94609-1809 |
| Country | United States of America |
| Sponsor | Novartis Pharmaceuticals Corporation (USA) |
| Address | One Health Plaza |
| City/town | East Hanover |
| Zip/Postcode | 07936 |
| Country | United States of America |
| Tel | +1 862 778 2791 |
| Fax | +1 973 781 5511 |
| halyna.wysowskyj@pharma.novartis.com | |
| Date applied | 23/07/2003 |
| Last edited | 08/09/2008 |
| Date ISRCTN assigned | 05/09/2003 |
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| © 2012 ISRCTN unless otherwise stated. | |
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