Selonsertib in Adults With Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Placebo; Selonsertib
Intervention description: Tablet administered orally once daily; Tablets administered orally once daily
Intervention MeSH terms: Selonsertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 151.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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
                  (<) 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

        Key Exclusion Criteria:

          -  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.