Beta-ThalassemiaPhase 2SIRTHALACLINNCT03877809
Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients
A Phase 2 study testing Sirolimus 0.5 mg in people with Beta-Thalassemia, run by Rare Partners srl Impresa Sociale at 2 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Beta-Thalassemia
- What is being tested?
- Sirolimus 0.5 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesItaly
- Study dates
- 27 Jun 2019to 30 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Patient treated with hydroxyurea at selection visit or in the last 6 months;
- Ongoing treatment with drugs possibly affecting sirolimus actions;
- Documented aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) at selection;
- Documented Platelet count <150.000/microliter and >1.000.000/microliter at selection;
- Heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher;
- Uncontrolled hypertension defined as systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg;
Show all 24Show fewer
- Significant arrhythmia requiring treatment,
- Corrected QT interval> 450 msec on selection ECG;
- Ejection fraction <50% by echocardiogram, multiple gated acquisition scan or cardiac magnetic resonance;
- Myocardial infarction within 6 months prior of selection;
- Positivity for human immunodeficiency virus (HIV) antibody, active hepatitis B (HBV) or hepatitis C (HCV) as demonstrated by the presence of hepatitis B surface antigen (HBsAg) and a positive HCV-RNA test, HBcAb and HBV-DNA positivity
- White blood cell [WBC] count <3000 cells per μL and/or Granulocytes <1500/mm3;
- Total cholesterol > 240 mg/dl;
- Triglycerides > 200 mg/dl;
- Proteinuria with urinary protein >1g/24 hrs;
- Current participation in another trial with investigational drug or experimental device, or inclusion in another trial with investigational drug or experimental device within the preceding month;
- Major surgery (including splenectomy) within 60 days before selection (patients must have fully recovered from any previous surgery);
- Iron chelation therapy changed in the last 3 months prior to selection (note that Deferiprone is not accepted as a chelation therapy drug in this study while Desferioxamine and Deferasirox are tolerated at stable dose);
- Current treatment with macrolide antibiotics (clarithromycin);
- Pregnant or lactating women;
- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the experimental drug;
- Treatment with live vaccines within 90 days preceding the selection;
- Subject with history or current malignancies (solid tumors and haematological malignancies) or presence of masses/tumor detected by ultrasound at selection;
- Subject with any significant medical condition and/or laboratory abnormality considered by the investigator as not adequately controlled at the time of selection.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology
Ferrara, 44121
Department of Growth and Reproduction Azienda Ospedaliero-Universitaria S.Anna
Ferrara, 44124
About this study
Official title: A Personalized Medicine Approach for Beta-thalassemia Transfusion Dependent Patients: Testing SIROLIMUS in a First Pilot Clinical Trial
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.
Read the detailed description
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:
- 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 objectives:
- 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.
- Conditions
- Beta-Thalassemia
- Being tested
- Sirolimus 0.5 mg
- Keywords
- Fetal hemoglobin, Sirolimus, Red Blood Cells
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus 0.5 mgDrug
Daily administration of 1 or more tablets
| Study group | Role | What they receive |
|---|---|---|
| Open label trial | Experimental | Sirolimus 0.5 mg tablets Receives: Drug: Sirolimus 0.5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 360 days
Secondary outcomes (10)
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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.
Measured: 360 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2019
- Study start27 Jun 2019
- Primary completion30 Apr 2022
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Interventional, pilot, single centre, open-label phase II study with sirolimus in patients with transfusion dependent beta-thalassemia
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rare Partners srl Impresa Sociale
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli Studi di Ferrara
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03877809
- Sponsor's protocol ID
- CT2-02-17
- Other IDs
- 2018-001942-33, 208872/Z/17/Z, 2018
- Acronym
- SIRTHALACLIN
- Status last verified
- Jan 2024
- First submitted
- 14 Mar 2019
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
Publications
Zuccato C, Cosenza LC, Zurlo M, Gasparello J, Papi C, D'Aversa E, Breveglieri G, Lampronti I, Finotti A, Borgatti M, Scapoli C, Stievano A, Fortini M, Ramazzotti E, Marchetti N, Prosdocimi M, Gamberini MR, Gambari R. Expression of gamma-globin genes in beta-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin). Ther Adv Hematol. 2022 Jun 21;13:20406207221100648. doi: 10.1177/20406207221100648. eCollection 2022.
PubMed 35755297Zurlo M, Finotti A, Gamberini MR, Gambari R. Co-Induction of ULK-1 and AHSP mRNAs in Erythroid Precursor Cells Isolated From a Sirolimus-Treated beta-Thalassemia Patient: A Case Report Study. Br J Biomed Sci. 2025 Jun 27;82:14311. doi: 10.3389/bjbs.2025.14311. eCollection 2025.
PubMed 40655320Zurlo M, Nicoli F, Proietto D, Dallan B, Zuccato C, Cosenza LC, Gasparello J, Papi C, d'Aversa E, Borgatti M, Scapoli C, Finotti A, Gambari R. Effects of Sirolimus treatment on patients with beta-Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells. J Cell Mol Med. 2023 Feb;27(3):353-364. doi: 10.1111/jcmm.17655. Epub 2023 Jan 10.
PubMed 36625233
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Personalized Medicine Approach for Beta-thalassemia Transfusion Dependent Patients: Testing SIROLIMUS in a First Pilot Clinical Trial
- ClinicalTrials.gov ID
- NCT03877809
- Acronym / sponsor ID
- SIRTHALACLIN / CT2-02-17
- Conditions
- Beta-Thalassemia
- Keywords
- Fetal hemoglobin, Sirolimus, Red Blood Cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Rare Partners srl Impresa SocialeUniversity, hospital or other
- Collaborators
- Università degli Studi di Ferrara
- Study start
- 27 Jun 2019 (actual)
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 18 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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 objectives:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Interventional, pilot, single centre, open-label phase II study with sirolimus in patients with transfusion dependent beta-thalassemia
| Arm | Type | Receives |
|---|---|---|
| Open label trial | Experimental | Drug: Sirolimus 0.5 mgSirolimus 0.5 mg tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (24 listed)
- Patient treated with hydroxyurea at selection visit or in the last 6 months;
- Ongoing treatment with drugs possibly affecting sirolimus actions;
- Documented aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) at selection;
- Documented Platelet count <150.000/microliter and >1.000.000/microliter at selection;
- Heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sirolimus 0.5 mgDaily administration of 1 or more tablets | Drug | Open label trial |
Primary outcome
Change from baseline of fetal hemoglobin level
Time frame: 360 days
Fetal hemoglobin level in peripheral blood at day 360 compared to day 0, assessed through high pressure liquid chromatography (HPLC)
10 secondary outcomes
Change from baseline of fetal hemoglobin level
Time frame: 180 days
Change from baseline of γ-globin expression
Time frame: 360 days
Change from baseline of biomarkers for erythropoiesis
Time frame: 360 days
Change from baseline of biomarkers for erythropoiesis
Time frame: 360 days
Change from baseline of biomarkers for haemolysis
Time frame: 360 days
Change from baseline of biomarkers for haemolysis
Time frame: 360 days
Change from baseline of tranfusion needs
Time frame: 360 days
Change from baseline of Iron status
Time frame: 360 days
Change from baseline of Immune function
Time frame: 360 days
Change from baseline of Quality of Life
Time frame: 360 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Results publication: PubMed 35755297Zuccato C, Cosenza LC, Zurlo M, Gasparello J, Papi C, D'Aversa E, Breveglieri G, Lampronti I, Finotti A, Borgatti M, Scapoli C, Stievano A, Fortini M, Ramazzotti E, Marchetti N, Prosdocimi M, Gamberini MR, Gambari R. Expression of gamma-globin genes in beta-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin). Ther Adv Hematol. 2022 Jun 21;13:20406207221100648. doi: 10.1177/20406207221100648. eCollection 2022.
- Derived from this study: PubMed 40655320Zurlo M, Finotti A, Gamberini MR, Gambari R. Co-Induction of ULK-1 and AHSP mRNAs in Erythroid Precursor Cells Isolated From a Sirolimus-Treated beta-Thalassemia Patient: A Case Report Study. Br J Biomed Sci. 2025 Jun 27;82:14311. doi: 10.3389/bjbs.2025.14311. eCollection 2025.
- Derived from this study: PubMed 36625233Zurlo M, Nicoli F, Proietto D, Dallan B, Zuccato C, Cosenza LC, Gasparello J, Papi C, d'Aversa E, Borgatti M, Scapoli C, Finotti A, Gambari R. Effects of Sirolimus treatment on patients with beta-Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells. J Cell Mol Med. 2023 Feb;27(3):353-364. doi: 10.1111/jcmm.17655. Epub 2023 Jan 10.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus 0.5 mg in people with Beta-Thalassemia, run by Rare Partners srl Impresa Sociale at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of fetal hemoglobin level (time frame: 360 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03877809, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.