A Phase 2 interventional study of Sirolimus 0.5 mg in Beta-Thalassemia, sponsored by Rare Partners srl Impresa Sociale. Completed at 2 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-01-23.
Sponsored by Rare Partners srl Impresa Sociale · Phase 2, Interventional, and Treatment
Beta-thalassemias are hereditary blood disorders caused by reduced or absent synthesis of hemoglobin beta chains, with variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Treatment is symptomatic and thalassemia is a major unmet medical need. Survival is increased, even in patients needing transfusions, in comparison with a few years ago, but the quality of life is poor for many patients. In some patients, an anomalous expression of gamma-globin genes has been observed, with a consequent rise in Fetal Hemoglobin levels. The patients displaying a clinical phenotype known as Hereditary Persistence of Fetal Hemoglobin (HPFH) exhibit a positive clinical status. To mimick HPFH, several compounds able to induce expression of fetal hemoglobins (HbF) have been evaluated. Within this framework, sirolimus is particularly interesting as an inducer of HbF. It has been used for many years for different indications and the available preclinical evidence warrant the start of a clinical development plan in thalassemia. The investigators propose a clinical trial in beta-thalassemia patients, designed to evaluate the effect of sirolimus on several parameters related to red blood cell status and to the level of HbF in particular, as a first step for the full clinical development in this new indication.
The general aim of the protocol is to demonstrate the applicability of a personalised and precision medicine approach in beta-thalassemia in a clinical trial setting for a repurposed drug, namely sirolimus. The presence of high level of Fetal Hemoglobin (HbF) is considered a condition predictive of a favourable outcome in thalassemia and its increase induced by pharmacological agents is considered a potential way to improve clinical status of the patients. In the present trial, 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 enrollment of 26 is below the median of 37 across 277 interventional studies indexed under Thalassemia.
Browse Thalassemia studies →This is the only study on the registry with Rare Partners srl Impresa Sociale as lead sponsor.
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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: 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: 360 days
Change from baseline of biomarkers for erythropoiesis
- - Evaluation of the biomarkers for erythropoiesis level at day 180 and 360 compared to baseline. Biomarkers will include: Reticulocytes count, Nucleated red blood cells count
Time frame: 360 days
Change from baseline of biomarkers for erythropoiesis
- - Evaluation of the biomarkers for erythropoiesis level at day 180 and 360 compared to baseline. Biomarkers will include: erythropoietin level, serum transferrin receptor level.
Time frame: 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: 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: 360 days
Change from baseline of tranfusion needs
- Measurement of the total blood quantity (in mL) transfused and 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 * Evaluation of serum ferritin level at day 90, 180 and 360 in comparison with day 0
Time frame: 360 days
Change from baseline of Immune function
* Peripheral blood immunophenotype-Lymphocyte subsets at day 90 and 360 compared to day 0 * Quantitative analysis of ImmunoglobulinG/ImmunoglobulinA/ImunoglobulinM at day 90 and 360 compared to day 0
Time frame: 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, Csr
This study is completed, as verified in Jan 2024. You cannot join it, but the record below documents what was studied.
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