Selonsertib in Adults With Pulmonary Arterial Hypertension

NCT02234141 | Completed Phase 2 Results DMC

• 2 other identifiers: GS-US-357-13942014-002131-34
• Study Type: interventional
• Target: 151
• Locations: 8 countries
• Sites: 46

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)

  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.

  Baseline to Week 24

Secondary Outcomes (18)

• 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 Other Cardiopulmonary Hemodynamic Measures: mRAP

  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

Study Arms (4)

Selonsertib 2 mg

EXPERIMENTAL

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

Drug: Selonsertib

Selonsertib 6 mg

EXPERIMENTAL

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

Drug: Selonsertib

Selonsertib 18 mg

EXPERIMENTAL

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

Drug: Selonsertib

Placebo

EXPERIMENTAL

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.

Drug: Placebo; Drug: Selonsertib

Interventions

Placebo DRUG

Tablet administered orally once daily

Also known as: GS-4997

Placebo

Selonsertib DRUG

Tablets administered orally once daily

Also known as: GS-4997

Placebo; Selonsertib 18 mg; Selonsertib 2 mg; Selonsertib 6 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (46)

University of South Alabama Medical Center

Mobile, Alabama, United States

Location

Advanced Lung Disease Institute

Phoenix, Arizona, United States

Location

Arizona Pulmonary Specialist, Ltd

Phoenix, Arizona, United States

Location

University of Arizona Clinical and Translational Science (CATS) Research Center

Tucson, Arizona, United States

Location

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

Location

University of California, Davis

Sacramento, California, United States

Location

University of California, San Francisco

San Francisco, California, United States

Location

LA Biomedical Research Institute Harbor-UCLA Medical Center

Torrance, California, United States

Location

University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion

Aurora, Colorado, United States

Location

The Emory Clinic

Atlanta, Georgia, United States

Location

University of Chicago Medicine

Chicago, Illinois, United States

Location

Boston University Medical Center

Boston, Massachusetts, United States

Location

Tufts Medical Center

Boston, Massachusetts, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, United States

Location

University of Minnesota

Minneapolis, Minnesota, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Mary M. Parkes Center // University of Rochester Medical Center

Rochester, New York, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Martha Morehouse Medical Pavilion

Columbus, Ohio, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Location

UT Southwestern Medical Center

Dallas, Texas, United States

Location

Inova Fairfax Medical Campus

Falls Church, Virginia, United States

Location

Peter Lougheed Center

Calgary, Alberta, Canada

Location

Vancouver General Hospital, The Lung Centre // Vancouver Coastal Health, Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Victoria Hospital - London Health Sciences Centre

London, Ontario, Canada

Location

University Health Network

Toronto, Ontario, Canada

Location

Institut Universitaire de caridologie et de pneumologie de Quebee (IUCPQ)

Sainte-Foy, Quebec, Canada

Location

CHU de Grenoble Clinique Universitaire de Pneumologie

Grenoble, France

Location

CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire

Le Kremlin-Bicêtre, France

Location

Hopital Cardiologique-CHRU Lille, Service de cardiologie

Lille, France

Location

Universitatsklinikul Giessen und Marburg GmbH

Giessen, Hesse, Germany

Location

Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln

Cologne, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitatsklinikum Leipzig

Leipzig, Germany

Location

Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg

Regensburg, Germany

Location

Universita "Sapienza"-Azienda Policlinico Umberto 1

Rome, Italy

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Doce (12) de Octubre

Madrid, Spain

Location

Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital

Clydebank, West Dunbartonshire, United Kingdom

Location

Royal Free Hampstead NHS Trust

London, United Kingdom

Location

Clinical Research Facility, Royal Hallamshrie Hospital

Sheffield, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34425071 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

selonsertib

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 9, 2014
• Study Start: November 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 10, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-03

Locations

US (24); IT (1); GB (3); FR (3); NL (1); ES (3); CA (5); DE (6)