Study protocol for a randomized, double-blind, placebo-controlled clinical trial of desidustat oral tablet in sickle...

Sickle cell disease (SCD) is a genetic disorder characterized by chronic hemolysis and vaso-occlusive crises. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), has shown promise in treating SCD by stimulating erythropoietin production in a similar manner that happens in response to hypoxia, promoting erythropoiesis and improving iron metabolism, leading to increased hemoglobin and RBC indices.

This was a phase IIa, double-blind, randomized, placebo-controlled, parallel-group, proof-of-concept, multicenter clinical trial designed to evaluate the efficacy and safety of desidustat in Indian adults with sickle cell disease (SCD). A total of 24 participants were enrolled based on predefined eligibility criteria, with 8 subjects per dose cohort (50 mg, 100 mg, and 150 mg), randomized in a 3:1 ratio (desidustat:placebo). The study included a screening period of up to 4 weeks, an 8-week treatment phase, and a follow-up visit at week 10, totaling 98 days. Efficacy (hemoglobin response rate) was assessed at week 8 relative to baseline compared to placebo. Dose adjustment of desidustat at week 4 was guided by hemoglobin levels measured using a calibrated HemoCue instrument.

Management of sickle cell disease (SCD) has limited treatment modalities available like hydroxyurea and blood transfusions. They offer benefits but their limitations underscore the ongoing need for safer, more effective, and accessible treatments. This proof-of-concept trial was conducted to investigate the efficacy and safety of desidustat oral tablet, 3 times per week for 8 weeks in SCD patients. Results from this trial could aid in establishing a cost-efficient therapeutic option for managing rare diseases like SCD.

The study was approved by Central Drugs Standard Control Organization (CDSCO: CT NOC number CT/SND/27/2023, protocol number DESI.23.001, version no. 01 registered on 12 June 2023) and was conducted for a new drug as per the GCP guidelines. The first subject was screened on 7 January 2025 and the last visit of the last subject was conducted on 31 July 2025, followed by clinical study report finalization on 29 September 2025.