Selonsertib in Adults With Pulmonary Arterial Hypertension

NCT ID: NCT02234141

Last Updated: 2019-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Selonsertib

Intervention Type: DRUG

Tablets administered orally once daily

Selonsertib 6 mg

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

Group Type: EXPERIMENTAL

Selonsertib

Intervention Type: DRUG

Tablets administered orally once daily

Selonsertib 18 mg

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

Group Type: EXPERIMENTAL

Selonsertib

Intervention Type: DRUG

Tablets administered orally once daily

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablet administered orally once daily

Selonsertib

Intervention Type: DRUG

Tablets administered orally once daily

Interventions

Placebo

Tablet administered orally once daily

Intervention Type: DRUG

Selonsertib

Tablets administered orally once daily

Intervention Type: DRUG

Other Intervention Names

GS-4997; GS-4997

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of South Alabama Medical Center

Mobile, Alabama, United States

Advanced Lung Disease Institute

Phoenix, Arizona, United States

Arizona Pulmonary Specialist, Ltd

Phoenix, Arizona, United States

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

Tucson, Arizona, United States

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

University of California, Davis

Sacramento, California, United States

University of California, San Francisco

San Francisco, California, United States

LA Biomedical Research Institute Harbor-UCLA Medical Center

Torrance, California, United States

University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion

Aurora, Colorado, United States

The Emory Clinic

Atlanta, Georgia, United States

University of Chicago Medicine

Chicago, Illinois, United States

Boston University Medical Center

Boston, Massachusetts, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

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

Rochester, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Martha Morehouse Medical Pavilion

Columbus, Ohio, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Inova Fairfax Medical Campus

Falls Church, Virginia, United States

Peter Lougheed Center

Calgary, Alberta, Canada

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

Vancouver, British Columbia, Canada

Victoria Hospital - London Health Sciences Centre

London, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

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

Sainte-Foy, Quebec, Canada

CHU de Grenoble Clinique Universitaire de Pneumologie

Grenoble, , France

CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire

Le Kremlin-Bicêtre, , France

Hopital Cardiologique-CHRU Lille, Service de cardiologie

Lille, , France

Universitatsklinikul Giessen und Marburg GmbH

Giessen, Hesse, Germany

Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg

Regensburg, , Germany

Universita "Sapienza"-Azienda Policlinico Umberto 1

Rome, , Italy

VU University Medical Center

Amsterdam, , Netherlands

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Doce (12) de Octubre

Madrid, , Spain

Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital

Clydebank, West Dunbartonshire, United Kingdom

Royal Free Hampstead NHS Trust

London, , United Kingdom

Clinical Research Facility, Royal Hallamshrie Hospital

Sheffield, , United Kingdom

Countries

United States; Canada; France; Germany; Italy; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34425071 (View on PubMed)

Other Identifiers

2014-002131-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-357-1394

Identifier Type: -

Identifier Source: org_study_id