Clinical trial NCT02234141: Selonsertib in Adults With Pulmonary Arterial Hypertension
Official title: A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Study of GS-4997 in Subjects With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-09-09
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in 6MWD Test
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in BDI After the 6MWD Test
timeFrame: Baseline to Week 24
measure: Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in NT-proBNP
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test
timeFrame: Baseline to Week 24
measure: Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE
timeFrame: Baseline to Week 24
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)
timeFrame: Baseline to Week 24
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)
timeFrame: Baseline to Week 24
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)
timeFrame: Baseline to Week 24
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Advanced Lung Disease Institute
state: Arizona
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialist, Ltd
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Clinical and Translational Science (CATS) Research Center
state: Arizona
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Torrance
country: United States
facility: LA Biomedical Research Institute Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion
state: Colorado
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: Mary M. Parkes Center // University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Martha Morehouse Medical Pavilion
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Calgary
country: Canada
facility: Peter Lougheed Center
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital, The Lung Centre // Vancouver Coastal Health, Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: Victoria Hospital - London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Sainte Foy
country: Canada
facility: Institut Universitaire de caridologie et de pneumologie de Quebee (IUCPQ)
state: Quebec
city: Grenoble Cedex 9
country: France
facility: CHU de Grenoble Clinique Universitaire de Pneumologie
city: Le Kremlin Bicetre Cedex
country: France
facility: CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire
city: Lille Cedex
country: France
facility: Hopital Cardiologique-CHRU Lille, Service de cardiologie
city: Giessen
country: Germany
facility: Universitatsklinikul Giessen und Marburg GmbH
state: Hessen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Koln
country: Germany
facility: Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Regensburg
country: Germany
facility: Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg
city: Rome
country: Italy
facility: Universita "Sapienza"-Azienda Policlinico Umberto 1
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Doce (12) de Octubre
city: Clydebank
country: United Kingdom
facility: Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital
state: West Dunbartonshire
city: London
country: United Kingdom
facility: Royal Free Hampstead NHS Trust
city: Sheffield
country: United Kingdom
facility: Clinical Research Facility, Royal Hallamshrie Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Rosenkranz S, Feldman J, McLaughlin VV, Rischard F, Lange TJ, White RJ, Peacock AJ, Gerhardt F, Ebrahimi R, Brooks G, Satler C, Frantz RP; ARROW Study Group. Selonsertib in adults with pulmonary arterial hypertension (ARROW): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2022 Jan;10(1):35-46. doi: 10.1016/S2213-2600(21)00032-1. Epub 2021 Aug 20.