Selonsertib in Adults With Pulmonary Arterial Hypertension (ARROW)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Selonsertib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02234141

2014-002131-34 (EudraCT Number)

GS-US-357-1394

Details and patient eligibility

About

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.

Enrollment: 151 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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151 participants in 4 patient groups

Selonsertib 2 mg

Experimental group

Description:

Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.

Treatment:

Drug: Selonsertib

Selonsertib 6 mg

Experimental group

Description:

Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.

Treatment:

Drug: Selonsertib

Selonsertib 18 mg

Experimental group

Description:

Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.

Treatment:

Drug: Selonsertib

Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Selonsertib