A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Study of GS-4997 in Subjects With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 46
- 主要终点
- Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 (<) 500 dynes*sec/cm^5, or PCWP/LVEDP ≤ 15 mm Hg if PVR ≥ 500 dynes•sec/cm^5
- •Be able to walk a distance of at least 100 meters
- •Have World Health Organization (WHO) Functional Class II or III symptoms
- •Meet the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to screening, performed with or without bronchodilation:
- •Forced expiratory volume in one second (FEV1) ≥ 55 percent (%) of predicted normal
- •FEV1: forced vital capacity (FVC) ratio ≥ 0.60
- •Receiving treatment with one or more drugs approved for PAH for ≥ 12 consecutive weeks and at stable dose for ≥ 8 consecutive weeks
排除标准
- •Diagnosis of PAH associated with significant venous or capillary involvement (PCWP greater 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.
研究组 & 干预措施
Selonsertib 2 mg
Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.
干预措施: Selonsertib (Drug)
Selonsertib 6 mg
Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
干预措施: Selonsertib (Drug)
Selonsertib 18 mg
Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
干预措施: Selonsertib (Drug)
Placebo
Participants will receive selonsertib placebo for 24 weeks, and may then be rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase.
干预措施: Placebo (Drug)
Placebo
Participants will receive selonsertib placebo for 24 weeks, and may then be rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase.
干预措施: Selonsertib (Drug)
结局指标
主要结局
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
时间窗: Baseline to Week 24
PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
次要结局
- Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class(Baseline to Week 24)
- Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP(Baseline to Week 24)
- Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index(Baseline to Week 24)
- Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP(Baseline to Week 24)
- Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test(Baseline to Week 24)
- Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)(Baseline to Week 24)
- Change From Baseline at Week 24 in BDI After the 6MWD Test(Baseline to Week 24)
- Change From Baseline at Week 24 in NT-proBNP(Baseline to Week 24)
- Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale(Baseline to Week 24)
- Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score(Baseline to Week 24)
- Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)(Baseline to Week 24)
- Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)(Baseline to Week 24)
- Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)(Baseline to Week 24)
- Change From Baseline at Week 24 in 6MWD Test(Baseline to Week 24)
- Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1(Baseline up to Week 24)
- Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE(Baseline to Week 24)
- Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)(Baseline to Week 24)
- Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)(Baseline to Week 24)