Phase 2 N=151 Randomized Double-blind Treatment

Selonsertib in Adults With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT02234141 ↗

Enrolled (actual)

151

Serious AEs

29.7%

Results posted

Apr 2019

Primary outcome: Primary: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC) — 35; -28; -21; 6 dyne*sec/cm^5 — p== 0.214

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Placebo (Drug); Selonsertib (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Gilead Sciences
Primary completion: Apr 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)	35; -28; -21; 6	= 0.214
SECONDARY Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index	-0.1; 0.1; 0.0; 0.0	—
SECONDARY Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP	1; -1; -3; 0	—
SECONDARY Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP	1; 0; -1; 1	—
SECONDARY Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)	0.0; 0.1; 1.1; -2.0	—
SECONDARY Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)	-0.01; 0.00; -0.03; -0.01	—
SECONDARY Change From Baseline at Week 24 in 6MWD Test	4.7; 3.5; -15.9; -15.0	—
SECONDARY Change From Baseline at Week 24 in BDI After the 6MWD Test	-0.1; 0.1; 0.1; 0.3	—
SECONDARY Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class	7; 6; 5; 1; 27; 24	—
SECONDARY Change From Baseline at Week 24 in NT-proBNP	1.17; 1.01; 1.01; 1.25	—
SECONDARY Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale	0; 2; 0; 0	—
SECONDARY Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score	0; -1; 1; -1	—
SECONDARY Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test	4.0; 0.1; -3.0; 2.4	—
SECONDARY Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1	NA; NA; 225.0; 178.0	—
SECONDARY Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE	0.0; -0.1; 0.0; 0.0	—
SECONDARY Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)	1; 2; -1; 1	—
SECONDARY Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)	1; 0; 0; 0	—
SECONDARY Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)	0.08; 0.05; 0.01; -0.02	—
SECONDARY Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)	-0.3; 0.0; -1.1; -0.6	—

Summary

The primary objective of this study is to evaluate the effect of selonsertib (GS-4997) on pulmonary vascular resistance (PVR), as measured by right heart catheterization (RHC) in adults with pulmonary arterial hypertension (PAH). The study will consist of a 24-week placebo-controlled treatment period and a long-term selonsertib treatment period. Participants completing the 24-week placebo-controlled period will be eligible to receive active treatment with selonsertib in the long-term treatment period.

Eligibility Criteria

Key Inclusion Criteria

Diagnosis of idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), drug- and toxin-induced PAH, or PAH associated with connective tissue disease, human immunodeficiency virus (HIV) infection, or congenital heart defects (repaired greater than 1 year prior to Screening)
Meet all of the following hemodynamic criteria by means of a screening right heart catheterization (RHC) completed prior to randomization:
Mean pulmonary artery pressure (mPAP) of greater than or equal to (≥) 25 millimeters of mercury (mm Hg)
Pulmonary vascular resistance (PVR) ≥ 400 dyne* second/centimeter^5 (dynes*sec/cm^5)
Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of less than or equal to (≤) 12 mm Hg if PVR ≥ 400 and less than ( ] 15 mm Hg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects
Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 NICE classification
Left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic, valvular or constrictive heart disease
Uncontrolled hypertension (≥ 180/110 mm Hg) at Screening
End stage renal disease (receiving peritoneal dialysis, hemodialysis, or status after renal transplantation)
Severe liver disease (Child-Pugh Class C, with or without cirrhosis)

Individuals may be rescreened one additional time with prior notification to and approval by the sponsor.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02234141). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.