Sickle cell disease (an hereditary hemoglobinopathy)
Conditions
Interventions
Trade Name: Exjade
Product Name: Exjade
Product Code: EMEA/H/C/000670
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Sponsors
AMsterdam UMC-AMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Sickle cell disease diagnosis: HbSS, or HbSß0-thalassemia genotype 2. Age 18-65 years 3. Willing and able to provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Blood transfusion in the preceding four months 2. Already using iron chelation due to iron overload 3. Ferritin levels of <50 µg/L and/or transferrin saturation of < 0.20. 4. LDH of < 300 U/L 5. Pregnancy or the desire to get pregnant in the following 6 months 6. Impaired renal function of GFR < 60 ml/min/1,73m2 (CKD-EPI). 7. Known allergic reaction to deferasirox. 8. Other somatic or cognitive condition disturbing adherence to study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to investigate the safety and efficacy (effect on point of sickling en pain) of deferasirox in patients met SCD without iron overload. ;Secondary Objective: In addition, the effect on neutrophil activity and phenotype, adhesion of neutrophils and red blood cells, fatigue questionairres, and other exploratory endpoints.;Primary end point(s): The main endpoints of this study are safety and efficacy. -We will evaluate safety by analysis of adverse events, medication use and physical and laboratory examinations. -The primary efficacy endpoint will be the effect of deferasirox on sickling of red blood cells, measured as changes in Point of Sickling (PoS), as quantified by Oxygenscan. Other efficacy endpoints include: - the proportion of patients with decreases in hemoglobin S (HbS) % - oxidative stress as reflected by advanced glycation end-products (AGEs);Timepoint(s) of evaluation of this end point: T0: before start of treatment T1: after 2 weeks of treatment T2: after 4 weeks of treatment T3: after 6 weeks of treatment T4: 4 weeks after completing treatment (week 10) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate RBC degradation as expressed by phosphatidylserine (PS) exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes and hemoglobin - To evaluate the effect of deferasirox on RBC HbS percentage - Effect of deferasirox on levels of non-transferrin bound iron (NTBI) and labile plasma iron (LPI) - To evaluate the effect of deferasirox on oxidative stress as expressed by intracellular metabolomics - To evaluate the effect of deferasirox on in vitro adhesion of RBCs - To evaluate the effect of deferasirox on endothelial activation as reflected by plasma levels of soluble vascular adhesion molecule-1 (sVCAM-1) and von Willebrand factor antigen (VWF:Ag) - To evaluate the effect of deferasirox on neutrophil activation as measured with flow cytometry and in vitro NET formation;Timepoint(s) of evaluation of this end point: T0: before start of treatment T1: after 2 weeks of treatment T2: after 4 weeks of treatment T3: after 6 weeks of treatment T4: 4 weeks after completing treatment (week 10) | — |
Countries
Netherlands
Contacts
Public ContactErfan Nur
Amsterdam UMC-AMC
Outcome results
None listed