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

Phase 2

Completed

Conditions: Sickle cell disease (SCD)
Haematological Disorders
Sickle-cell disorders

Registration Number: ISRCTN05896089

Lead Sponsor: ovartis Pharmaceuticals Corporation (USA)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 195

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.

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 ß-blockers or angiotensin-converting enzyme inhibitors was permitted)
7. Chelation therapy-associated ocular toxicity

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety assessments:<br>1. Laboratory assessments: performed monthly and included complete blood counts with differential counts:<br>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)<br>1.2. Iron parameters (total iron, transferrin, transferrin saturation and ferritin)<br>1.3. Urinary testing performed on random collections (determination of creatinine, total protein and albumin) <br>2. Physical examinations (electrocardiograms [ECG], audiometry and ophthalmological tests) were performed at baseline, 12, 24, 36 and 52 weeks<br>3. In patients less than 16 years of age, additional assessments included growth velocity and pubertal stage

Secondary Outcome Measures

Name	Time	Method
Efficacy assessments:<br>1. Liver iron concentration: determined by superconducting quantum interference device (SQUID) biosusceptometry at baseline, 24 and 52 weeks<br>2. Serum ferritin: assessed monthly during the study and the change was determined using the baseline and final ferritin level<br><br>Compliance:<br>1. For deferasirox, compliance was assessed by counting the number of tablets returned in bottles at each visit<br>2. For deferoxamine, the numbers of vials returned at each visit were counted