beta-thalassemic patients MedDRA version: 20.0 Level: PT Classification code 10043391 Term: Thalassaemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
(-) - Rapamicina
Antibiotico AY 22989
Trade Name: RAPAMUNE 0.5 mg
Product Name: Sirolimus 0.5 mg
Product Code: Sirolimus 0.5 mg
Pharmaceutical Form: Coated tablet
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Other descriptive
Rapammune
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Sponsors
Rare Partners s.r.l. Impresa Sociale
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Responsive to the in vitro (ErPCs) treatment with Sirolimus according to laboratory specific definition (= 20% increase of HbF in comparison with samples not treated with Sirolimus) 2. AST or ALT 150.000/ul 4. Fertile women using an adequate system of contraception 5. Patients willing to follow all the study requirements and perform all the study visits and to cooperate with the investigator 6. Selection criteria must still be fulfilled at the time of the inclusion visit 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 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Uncontrolled hypertension defined as systolic pressure (PA) = 140 mm Hg or diastolic pressure = 90 mm Hg. 2. Class 3 or higher heart failure (New York Heart Association, NYHA). 3. QTc> 450 msec on selection ECG. 4. White blood cell [WBC] count 240 mg/dl 6. Triglycerides > 200 mg/dl 7. Proteinuria with urinary protein >1g/24 hrs; 8. Any active infection requiring parenteral antibiotic therapy within 28 days prior to inclusion or oral antibiotics within 14 days prior to inclusion; 9. Enrolment into one other drug or device trial since selection; 10. Major surgery (including splenectomy) performed after the study selection visit . 11. Ongoing treatment with drugs and agents that could increase the concentration of Sirolimus in the blood including: ciclosporin, bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, protease inhibitors (eg for HIV and hepatitis C which require pharmacological treatment with ritonavir, indinavir, boceprevir and telaprevir), metoclopramide, nicardipine, troleandomycin, verapamil. 12. Ongoing treatment with drugs and agents that could reduce the concentration of Sirolimus including carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's wort (Hypericum perforatum). 13. Cytotoxic agents, systemic corticosteroids, immunosuppressants or anticoagulant therapy such as warfarin or heparin within 28 days before inclusion (prophylactic aspirin up to 100 mg / day is allowed); 14. Macrolidic antibiotics (clarithromycin), ACE inhibitors. 15. Pregnant or lactating women. 16. Occurrence of an event which leads to the appearance of a non-selection criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the suitability of sirolimus for the treatment of beta-thalassemia patients within the frame of a comprehensive project aimed to the reduction of their transfusions need (consequently ameliorating their quality of life). This goal can be obtained through a pharmacologically mediated increased level of HbF, with a prerequisite to be verified, namely the correlation between induction of HbF in vitro and in vivo in single patients.;Secondary Objective: -To assess safety of sirolimus and correlation between administered dose and blood levels in beta-thalassemia patients, -To assess the influence of sirolimus on transfusion regimen -To assess the effect of sirolimus on hematopoietic and immune system of thalassemia patients. ;Primary end point(s): HbF level in peripheral blood at day 360 compared to day 0, assessed through HPLC;Timepoint(s) of evaluation of this end point: for all study period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - HbF level in peripheral blood at days 90 and 180 compared to day 0, assessed through HPLC - Assessment of HbF level as % of HbF with respect to total hemoglobin production in ErPCs at day 90, 180 and 360 compared to day 0, - Level of induction of the ?-globin expression at day 90, 180 and 360 compared to day 0 - Haematic analysis and evaluation of the biomarkers for erythropoiesis and haemolysis level at day 180 and 360 compared to baseline. Biomarkers will be: Reticulocytes count, Nucleated red blood cells (NRBCs), serum lactate dehydrogenase (LDH), serum bilirubin level, erythropoietin level, serum transferrin receptor level. - Measurement of the total blood quantity (in mL) transfused and recording of the number of transfusion done in a semester (day -360 to -180, day -180 to 0, day 0 to 180, day 180 to 360) - Evaluation of the intake of iron chelators at days 180 and 360 compared to baseline - Evaluation of serum ferritin level at day 90, 180 and 360 in comparison with day 0 - Peripheral blood immunophenotype-Lymphocyte subsets at day 90 and 360 compared to day 0 - Quantitative analysis of IgG/IgA/IgM at day 90 and 360 compared to day 0 - Evaluation of the patient quality of life at 6 and 12 months compared to baseline through TranQoL questionnaire ;Timepoint(s) of evaluation of this end point: for all study period | — |
Countries
Italy
Contacts
Public ContactDr. Marco PROSDOCIMI
RARE PARTNERS srl IMPRESA SOCIALE
Outcome results
None listed