NCT03877809: SIRTHALACLIN

Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients

Completed Phase 2 Last updated 23 January 2024

What this trial tests

Phase 2 trial testing Sirolimus 0.5 mg in Beta-Thalassemia in 26 participants. Completed in 30 April 2022.

Timeline

27 June 2019

Primary endpoint
30 April 2022

30 April 2022

Quick facts

Lead sponsor	Rare Partners srl Impresa Sociale
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	26
Start date	27 June 2019
Primary completion	30 April 2022
Estimated completion	30 April 2022
Sites	2 locations across Italy

Drugs / interventions tested

• Sirolimus 0.5 mg — full drug profile →

Conditions studied

• Beta-Thalassemia — all drugs for Beta-Thalassemia →

Sponsor

Rare Partners srl Impresa Sociale — full company profile →

Who can join

Adults 18 to 65, any sex, with Beta-Thalassemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficient CRISPR-Cas9-based genome editing of β-globin gene on erythroid cells from homozygous β<sup>0</sup>39-thalassemia patients.
   Cosenza LC, Gasparello J, Romanini N, Zurlo M, et al · · 2021 · cited 34× · PMID 33997100 · DOI 10.1016/j.omtm.2021.03.025
2. Expression of γ-globin genes in β-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin).
   Zuccato C, Cosenza LC, Zurlo M, Gasparello J, et al · · 2022 · cited 22× · PMID 35755297 · DOI 10.1177/20406207221100648
3. Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with <i>Cinchona</i> Alkaloids: Induction of Fetal Hemoglobin Production.
   Zuccato C, Cosenza LC, Zurlo M, Lampronti I, et al · · 2021 · cited 21× · PMID 34948226 · DOI 10.3390/ijms222413433
4. β-Thalassemia: evolving treatment options beyond transfusion and iron chelation.
   Langer AL, Esrick EB. · · 2021 · cited 18× · PMID 34889443 · DOI 10.1182/hematology.2021000313
5. Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications.
   Gambari R, Waziri AD, Goonasekera H, Peprah E. · · 2024 · cited 14× · PMID 38673849 · DOI 10.3390/ijms25084263
6. Rapamycin in Cerebral Cavernous Malformations: What Doses to Test in Mice and Humans.
   Hagan MJ, Shenkar R, Srinath A, Romanos SG, et al · · 2022 · cited 13× · PMID 35592432 · DOI 10.1021/acsptsci.2c00006
7. A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs.
   Prosdocimi M, Zuccato C, Cosenza LC, Borgatti M, et al · · 2022 · cited 10× · PMID 36110836 · DOI 10.12688/wellcomeopenres.17845.3
8. Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management.
   Traeger-Synodinos J, Vrettou C, Sofocleous C, Zurlo M, et al · · 2024 · cited 9× · PMID 38542374 · DOI 10.3390/ijms25063400