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Selonsertib in Adults With Pulmonary Arterial Hypertension (ARROW)

Primary Purpose

Pulmonary Arterial Hypertension

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Selonsertib
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of South Alabama Medical Center
  • Advanced Lung Disease Institute
  • Arizona Pulmonary Specialist, Ltd
  • University of Arizona Clinical and Translational Science (CATS) Research Center
  • VA Greater Los Angeles Healthcare System
  • University of California, Davis
  • University of California, San Francisco
  • LA Biomedical Research Institute Harbor-UCLA Medical Center
  • University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion
  • The Emory Clinic
  • University of Chicago Medicine
  • Boston University Medical Center
  • Tufts Medical Center
  • University of Michigan Health System
  • University of Minnesota
  • Mayo Clinic
  • Washington University School of Medicine
  • Mary M. Parkes Center // University of Rochester Medical Center
  • Cleveland Clinic
  • Martha Morehouse Medical Pavilion
  • Allegheny General Hospital
  • UPMC Presbyterian Hospital
  • UT Southwestern Medical Center
  • Inova Fairfax Medical Campus
  • Peter Lougheed Center
  • Vancouver General Hospital, The Lung Centre // Vancouver Coastal Health, Vancouver General Hospital
  • Victoria Hospital - London Health Sciences Centre
  • University Health Network
  • Institut Universitaire de caridologie et de pneumologie de Quebee (IUCPQ)
  • CHU de Grenoble Clinique Universitaire de Pneumologie
  • CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire
  • Hopital Cardiologique-CHRU Lille, Service de cardiologie
  • Universitatsklinikul Giessen und Marburg GmbH
  • Universitätsklinikum Carl Gustav Carus
  • Medizinische Hochschule Hannover
  • Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln
  • Universitatsklinikum Leipzig
  • Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg
  • Universita "Sapienza"-Azienda Policlinico Umberto 1
  • VU University Medical Center
  • Hospital Clinic de Barcelona
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario Doce (12) de Octubre
  • Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital
  • Royal Free Hampstead NHS Trust
  • Clinical Research Facility, Royal Hallamshrie Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Selonsertib 2 mg

Selonsertib 6 mg

Selonsertib 18 mg

Placebo

Arm Description

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

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

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index
Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. 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.
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP
mPAP is the mean blood pressure in the pulmonary artery. 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.
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP
mRAP is the mean blood pressure in the right atrium of the heart. 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.
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)
SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. 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.
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)
RVCP is a cardiopulmonary hemodynamic assessment. 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.
Change From Baseline at Week 24 in 6MWD Test
The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. 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.
Change From Baseline at Week 24 in BDI After the 6MWD Test
Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number > 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. 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.
Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class
Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.
Change From Baseline at Week 24 in NT-proBNP
NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. 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.
Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale
Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. 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.
Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score
Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. 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.
Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test
HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. 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.
Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1
TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both > 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE
TAPSE is an echocardiographic assessment of right ventricular function. 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.
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)
Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. 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.
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)
TAS is an echocardiographic assessment of right ventricular function. 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.
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)
The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. 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.
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)
RVFAC is an echocardiographic assessment of right ventricular function. 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.

Full Information

First Posted
September 2, 2014
Last Updated
March 19, 2019
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02234141
Brief Title
Selonsertib in Adults With Pulmonary Arterial Hypertension
Acronym
ARROW
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

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selonsertib 2 mg
Arm Type
Experimental
Arm Description
Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.
Arm Title
Selonsertib 6 mg
Arm Type
Experimental
Arm Description
Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
Arm Title
Selonsertib 18 mg
Arm Type
Experimental
Arm Description
Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
Arm Title
Placebo
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
GS-4997
Intervention Description
Tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Selonsertib
Other Intervention Name(s)
GS-4997
Intervention Description
Tablets administered orally once daily
Primary Outcome Measure Information:
Title
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
Description
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.
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index
Description
Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP
Description
mPAP is the mean blood pressure in the pulmonary artery. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP
Description
mRAP is the mean blood pressure in the right atrium of the heart. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)
Description
SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)
Description
RVCP is a cardiopulmonary hemodynamic assessment. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in 6MWD Test
Description
The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in BDI After the 6MWD Test
Description
Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number > 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. 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.
Time Frame
Baseline to Week 24
Title
Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class
Description
Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in NT-proBNP
Description
NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale
Description
Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score
Description
Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test
Description
HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. 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.
Time Frame
Baseline to Week 24
Title
Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1
Description
TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both > 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.
Time Frame
Baseline up to Week 24
Title
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE
Description
TAPSE is an echocardiographic assessment of right ventricular function. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)
Description
Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)
Description
TAS is an echocardiographic assessment of right ventricular function. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)
Description
The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. 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.
Time Frame
Baseline to Week 24
Title
Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)
Description
RVFAC is an echocardiographic assessment of right ventricular function. 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.
Time Frame
Baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of South Alabama Medical Center
City
Mobile
State/Province
Alabama
Country
United States
Facility Name
Advanced Lung Disease Institute
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Arizona Pulmonary Specialist, Ltd
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
University of Arizona Clinical and Translational Science (CATS) Research Center
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
VA Greater Los Angeles Healthcare System
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
Country
United States
Facility Name
LA Biomedical Research Institute Harbor-UCLA Medical Center
City
Torrance
State/Province
California
Country
United States
Facility Name
University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
The Emory Clinic
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Mary M. Parkes Center // University of Rochester Medical Center
City
Rochester
State/Province
New York
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Martha Morehouse Medical Pavilion
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
UPMC Presbyterian Hospital
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Inova Fairfax Medical Campus
City
Falls Church
State/Province
Virginia
Country
United States
Facility Name
Peter Lougheed Center
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Vancouver General Hospital, The Lung Centre // Vancouver Coastal Health, Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Victoria Hospital - London Health Sciences Centre
City
London
State/Province
Ontario
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Institut Universitaire de caridologie et de pneumologie de Quebee (IUCPQ)
City
Sainte Foy
State/Province
Quebec
Country
Canada
Facility Name
CHU de Grenoble Clinique Universitaire de Pneumologie
City
Grenoble Cedex 9
Country
France
Facility Name
CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire
City
Le Kremlin Bicetre Cedex
Country
France
Facility Name
Hopital Cardiologique-CHRU Lille, Service de cardiologie
City
Lille Cedex
Country
France
Facility Name
Universitatsklinikul Giessen und Marburg GmbH
City
Giessen
State/Province
Hessen
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln
City
Koln
Country
Germany
Facility Name
Universitatsklinikum Leipzig
City
Leipzig
Country
Germany
Facility Name
Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg
City
Regensburg
Country
Germany
Facility Name
Universita "Sapienza"-Azienda Policlinico Umberto 1
City
Rome
Country
Italy
Facility Name
VU University Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Doce (12) de Octubre
City
Madrid
Country
Spain
Facility Name
Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital
City
Clydebank
State/Province
West Dunbartonshire
Country
United Kingdom
Facility Name
Royal Free Hampstead NHS Trust
City
London
Country
United Kingdom
Facility Name
Clinical Research Facility, Royal Hallamshrie Hospital
City
Sheffield
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34425071
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.
Results Reference
derived

Learn more about this trial

Selonsertib in Adults With Pulmonary Arterial Hypertension

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