Study To Evaluate Voxelotor in Patients with Sickle Cell Disease
Research type
Research Study
Full title
A Phase 2, Open Label, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Voxelotor in Patients with Sickle Cell Disease
IRAS ID
271866
Contact name
Henry Fok
Contact email
Sponsor organisation
Global Blood Therapeutics, Inc.
Eudract number
2019-001838-34
Duration of Study in the UK
1 years, 6 months, 5 days
Research summary
Summary of Research
Sickle Cell Disease (SCD) is a rare and inherited disorder caused by a point mutation in the β-globin gene leading to formation of Haemoglobin S (HbS). It is devastating, and debilitating disease marked by the pathophysiologic features of hemolytic anemia, vaso-occlusion, and progressive end-organ damage, with a clinical course characterized by life-long disability and early death.
This single-center SCD study is an open-label, prospective study of the tolerability and safety of voxelotor 2000, 2500 and 3000 mg in adult participants with SCD ≥ 18 to < 60 years of age.
Haemoglobin (Hb) concentration is an important indicator of disease severity, indicating not only the degree of anemia but also the degree of hemolysis that occurs in patients with SCD
There are currently 2 approved therapies for the treatment of SCD: Hydroxyurea (HU)and L-glutamine (in US). However; despite the current standard of care, patients with SCD continue to suffer serious morbidity and premature mortality.
To date, no drugs have been approved that specifically and directly target HbS polymerization, the underlying mechanism of SCD and a significant unmet need remains in SCD for new mechanism based, preventive, and potentially disease-modifying therapies. Because oxyhemoglobin is a potent inhibitor of HbS, allosteric modification of Hb to increase the proportion of oxyhemoglobin, as is the case with voxelotor, is a promising strategy to achieve inhibition of HbS in all Red Blood Cells (RBCs), and clinically meaningful increase in Hb, as well as concurrent reductions in clinical measures of haemolysis.
In this study baseline response will be characterized in participants receiving a 9-week treatment regimen with voxelotor 1500 mg and compared, within and across participants, to the response with the highest dose level tolerated at steady state. 9 weeks was chosen because based on prior data this is a sufficient time period to achieve steady state on Hb and haemolysis parameters. Dose escalation will be done in 2 to 4 week increments to assess tolerability at the escalated dose.Summary of Results
GBT 440-029. Phase 2 study of the tolerability and safety of intra-subject dose escalation to cumulative daily voxelotor doses of 2000, 2500, and 3000 mg in adult subjects with SCD ≥ 18 to < 60 years of age.
The primary objective of this study was to evaluate the tolerability and safety of voxelotor at daily doses greater than 1500 mg (2000 to 3000 mg) in subjects with SCD.
Due to enrollment issues impacted by the coronavirus disease 2019 (COVID-19) pandemic, the decision to terminate the conduct of this study was made by the Sponsor.
Given that (1) there are no current plans to commercialize voxelotor at cumulative daily doses greater than 1500 mg, (2) the study was not designed to be label enabling, and (3) in consideration of the enrollment issues, the Sponsor elected to terminate the study.
The decision to terminate the study prior to planned completion was not based on any identified safety issues.
Due to the early study termination, no formal statistical or PK/PD analysis plans were written for this study. However, the overall planned analysis of the data is described.
Based on the limited data from this study, the safety profile of voxelotor at cumulative daily doses up to 3000 mg was consistent with the safety profile of the voxelotor 1500 mg once daily dose (Vichinsky, 2018).REC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/1583
Date of REC Opinion
5 Nov 2019
REC opinion
Further Information Favourable Opinion