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 |
| EudraCT/CTIS number | 2004-000597-31 |
| ClinicalTrials.gov number | NCT01090323 |
| Secondary identifying numbers | CICL670 0109 |
- 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
Scientific
Children's Hospital & Research Center at Oakland
747 52nd Street
OPC-PCRC, 1st Floor
Oakland
94609-1809
United States of America
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Deferasirox (ICL670), deferoxamine (DFO) |
| Primary outcome measure | 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 study start date | 01/01/2004 |
| Completion date | 01/01/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 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
- Canada
- France
- Italy
- United Kingdom
- United States of America
Study participating centre
Children's Hospital & Research Center at Oakland
Oakland
94609-1809
United States of America
94609-1809
United States of America
Sponsor information
Novartis Pharmaceuticals Corporation (USA)
Industry
Industry
One Health Plaza
East Hanover
07936
United States of America
| Phone | +1 (0)862 778 2791 |
|---|---|
| halyna.wysowskyj@pharma.novartis.com | |
"ROR" |
https://ror.org/028fhxy95 |
Funders
Funder type
Industry
Novartis Pharmaceuticals Corporation
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Novartis Pharmaceuticals Corp., Novartis United States, Novartis, NPC
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Results article | results | 01/02/2007 | Yes | No |
Editorial Notes
21/03/2016: added link to results - basic reporting.
