A Phase 2 interventional study of Sirolimus 0.5 mg in Beta-Thalassemia, sponsored by Università degli Studi di Ferrara. Status unknown at 4 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-11-12.
Sponsored by Università degli Studi di Ferrara · Phase 2, Interventional, and Treatment
In β-thalassaemia and Sickle Cell Disease (SCD), a significant production of fetal haemoglobin (HbF) may reduce the severity of clinical course and reactivation of γ-globin gene expression in adulthood. HbF induction is one of the best strategies to ameliorate the characteristic symptoms of these diseases. Hydroxyurea (HU) is the only medication, approved by the US Food and Drug Administration, inducing HbF. However, treatments with HU induce sufficient HbF levels in only half of the patients, and side effects including leukopenia and neutropenia are frequently reported. Therefore, novel therapeutic inducers must be identified to develop a personalized treatment in β-thalassaemia and sickle cell anaemia. The availability of new treatments depends on drugs already approved for other indications, and on pharmacokinetics and pharmacovigilance already assessed. Rapamycin (as Sirolimus) is an immunosuppressant agent, approved by the FDA for acute rejection prevention in renal transplant recipients. The ability of this drug to induce γ-globin gene expression in erythroleukemia cell line and erythroid precursors cells (ErPCs) in ß-thalassaemia patients is already known. A clinical investigation on the effects of sirolimus in ß-Thalassaemia aims to evaluate several parameters related to red blood cell status and HbF levels and is a first step for the full clinical development in this new indication.
The general aim of this protocol is to demonstrate the applicability of a personalised and precision medicine approach in beta-thalassaemia; the clinical trial setting repurposes a drug, namely sirolimus. The presence of high Fetal Hemoglobin (HbF) levels is considered a condition predictive of a favourable outcome in thalassaemia. Its increase induced by pharmacological agents is considered a potential way to improve the clinical status of the patients. In terms of efficacy analysis, the investigators will focus their attention on HbF levels.
Primary objective:
Secondary objectives:
416 studies on the registry are indexed under Thalassemia; 67 are open to participants now.
This study's planned enrollment of 45 is above the median of 37 across 277 interventional studies indexed under Thalassemia.
Browse Thalassemia studies →Università degli Studi di Ferrara is the lead sponsor of 64 studies on the registry; 10 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Note that patients will be treated with oral sirolimus only in the case their Erythroid Precursor Cells (ErPCs) are responsive to the in vitro treatment with sirolimus according to laboratory-specific definition (≥ 20% increase of HbF in comparison with samples not treated with sirolimus);
Exclusion Criteria:
Sirolimus 0.5 mg tablets
Drug: Sirolimus 0.5 mg
Daily administration of 1 or more tablets
Change from baseline of fetal hemoglobin level
Fetal hemoglobin level in peripheral blood at day 360 compared to day 0, assessed through high pressure liquid chromatography (HPLC)
Time frame: 360 days
Change from baseline of fetal hemoglobin level
Fetal hemoglobin level in peripheral blood at days 90 and 180 compared to day 0, assessed through HPLC
Time frame: 90-180 days
Change from baseline of γ-globin expression
Level of induction of the γ-globin expression at day 90, 180 and 360 compared to day 0
Time frame: 90-180-360 days
Change from baseline of biomarkers for erythropoiesis
- Evaluation of the Reticulocytes number at day 180 and 360 compared to baseline.
Time frame: 180-360 days
Change from baseline of biomarkers for erythropoiesis
- Evaluation of the Nucleated red blood cells number at day 180 and 360 compared to baseline.
Time frame: 180-360 days
Change from baseline of biomarkers for erythropoiesis
- Evaluation of the erythropoietin level at day 180 and 360 compared to baseline.
Time frame: 180-360 days
Change from baseline of biomarkers for erythropoiesis
- Evaluation of the serum transferrin receptor level at day 180 and 360 compared to baseline.
Time frame: 180-360 days
Change from baseline of biomarkers for haemolysis
- - Evaluation of the biomarkers for haemolysis level at day 180 and 360 compared to baseline. Biomarkers will include: serum bilirubin level
Time frame: 180-360 days
Change from baseline of biomarkers for haemolysis
- - Evaluation of the biomarkers for haemolysis level at day 180 and 360 compared to baseline. Biomarkers will include: serum lactate dehydrogenase (LDH) level
Time frame: 180-360 days
Change from baseline of tranfusion needs
Measurement of the total blood quantity (in mL) transfused (day -360 to -180, day -180 to 0, day 0 to 180, day 180 to 360)
Time frame: 360 days
Change from baseline of tranfusion needs
Recording of the number of transfusions done in a semester (day -360 to -180, day -180 to 0, day 0 to 180, day 180 to 360)
Time frame: 360 days
Change from baseline of Iron status
• Evaluation of the intake of iron chelators at days 180 and 360 compared to baseline
Time frame: 180-360 days
Change from baseline of Iron status
• Evaluation of serum ferritin level at day 90, 180 and 360 in comparison with day 0
Time frame: 90-180-360 days
Change from baseline of Immune function
• Peripheral blood immunophenotype-Lymphocyte subsets at day 90 and 360 compared to day 0
Time frame: 90-360 days
Change from baseline of Immune function
• Quantitative analysis of ImmunoglobulinG/ImmunoglobulinA/ImunoglobulinM at day 90 and 360 compared to day 0
Time frame: 90-360 days
Change from baseline of Quality of Life
Evaluation of the patient quality of life at 6 and 12 months compared to baseline through Transfusion-dependent Quality of Life questionnaire (TranQol), measuring specifically the quality of life in patients with thalassemia. The TranQol is a disease-specific Quality of Life measure that has been shown to be valid and reliable (Klaassen et al, British Journal of Haematology, 2014, 164, 431-437). On a total scale of 0-100, higher values always represent a better outcome. The questions are grouped into four domains: physical health, emotional health, family functioning, and school and career functioning. The adult self-report questionnaires include a fifth category on sexual activity which is only one item. Subscales are summed
Time frame: 360 days
Plan to share: Yes — At the end of the study the study protocol and the clinical trial report will be available to other researchers. Publication of the data is planned
Supporting information: Study protocol
No publications or documents are linked to this record.
This study is status unknown, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Università degli Studi di Ferrara