Abstract
Purpose Despite currently available therapy, the morbidity and mortality of pulmonary arterial hypertension (PAH) remains high. PAH is characterized by abnormal proliferation of pulmonary arterial smooth muscle cells, endothelial cells, and myofibroblasts. GB002 is a unique, highly potent, small molecule that targets PDGFRα/β, CSF1R, and c-KIT and modulates BMPR2, kinases implicated in the development of PAH. GB002 is formulated for inhalation delivery to directly target the diseased lung to limit systemic exposure and thereby potentially improve efficacy and tolerability. A Phase 2 study has been initiated to evaluate the efficacy and safety of inhaled GB002 in adult subjects with World Health Organization (WHO) Group 1 PAH. (NCT04456998). Methods This is a randomized, double-blind, placebo-controlled study. Patients with Functional Class II/III PAH on therapy and with a pulmonary vascular resistance (PVR) greater than or equal to 400 dyne•s/cm5 will be eligible. The planned treatment period is 24 weeks, with a target enrollment of 80 patients. Endpoints The primary endpoint is change in PVR measured by right heart catheterization from baseline to 24 weeks. The key secondary endpoint is change (baseline to 24 weeks) in 6-minute walk test (6MWT). Exploratory endpoints include quality of life, change in risk score, time to clinical worsening, and the following echocardiographic parameters: tricuspid annular systolic velocity, right ventricular (RV) Tei index and right ventricular free wall strain (RVFWS). Sub-studies include 6MWT heart rate expenditure change from baseline to 24 weeks, and changes in pulmonary arterial blood volume measured by CT imaging (baseline to 24 weeks). An Independent Data Monitoring Committee (IDMC) will ensure that benefits and risks remain acceptable during the conduct of the study. In this phase 2 study, the effects of GB002 on hemodynamics, 6MWT and other endpoints at 24 weeks will be assessed. Exploratory biomarkers will be evaluated for target engagement and response to treatment.
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