The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of osivelotor.
This is a three-part, multicenter, Phase 2/3 study of orally administered osivelotor in participants with sickle cell disease (SCD). Part A will evaluate the safety, tolerability, and efficacy of osivelotor in adult participants with SCD to determine an optimal dose. (Complete) Part B will evaluate the efficacy of osivelotor versus placebo in adult and adolescent participants with SCD for 48 weeks. Open Label Extension (OLE) will evaluate the long-term safety and hematologic responses of open-label osivelotor in adult and adolescent participants having completed Part B.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
389
Tablets which contain drug substance
Part A
Number of adult participants with change from baseline in hemoglobin (Hb) through week 12 as measured by change in osivelotor concentrations from baseline or percentage change from baseline of clinical measures of anemia Hb and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).
Time frame: Through week 12
Part B
Co-primary endpoints: Hb response (increase from baseline of \>1 g/dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48) and the Annualized rate of VOC through end of Week 48. A VOC is defined as an acute episode of pain that: * Has no medically determined cause other than a vaso-occlusive event, and * Results in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), and * Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. Complicated VOCs of acute chest syndrome (ACS), hepatic sequestration, splenic sequestration, priapism, and dactylitis that meet the requirements listed above will be included in this co-primary endpoint.
Time frame: Through week 48
OLE
Incidence of Treatment Emergent Adverse Events: * Incidence of SAEs * Incidence of AEs leading to discontinuation * Change from baseline in laboratory parameters.
Time frame: Approximately 24 months after last patient enrolled
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