Overview

This trial has been completed.

Condition pulmonary arterial hypertension
Treatments selonsertib, placebo
Phase phase 2
Sponsor Gilead Sciences
Start date November 2014
End date April 2016
Trial size 151 participants
Trial identifier NCT02234141, 2014-002131-34, GS-US-357-1394

Summary

This study will compare the efficacy, safety, and tolerability of three doses of selonsertib (GS-4997) to placebo 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive selonsertib 2 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
selonsertib GS-4997
Tablet administered orally once daily
(Experimental)
Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
selonsertib GS-4997
Tablet administered orally once daily
(Experimental)
Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
selonsertib GS-4997
Tablet administered orally once daily
(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.
selonsertib GS-4997
Tablet administered orally once daily
placebo
Tablets administered orally once daily

Primary Outcomes

Measure
Change from baseline in pulmonary vascular resistance at Week 24, as measured by right heart catheterization
time frame: Baseline; Week 24

Secondary Outcomes

Measure
Change from baseline at Week 24 in other cardiopulmonary hemodynamic measures
time frame: Baseline; Week 24
Change from baseline at Week 24 in 6-minute walk distance (6MWD)
time frame: Baseline; Week 24
Change from baseline at Week 24 in Borg Dyspnea index (BDI) immediately following exercise
time frame: Baseline; Week 24
Change from baseline at Week 24 in World Health Organization (WHO) Functional Class
time frame: Baseline; Week 24
Change from baseline at Week 24 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
time frame: Baseline; Week 24
Change from baseline at Week 24 in SF-36 Health Survey physical functioning scale
time frame: Baseline; Week 24
Change from baseline at Week 24 in emPHasis-10 questionnaire
time frame: Baseline; Week 24
Change from baseline at Week 24 in heart rate recovery after the 6-minute walk test (6MWT)
time frame: Baseline; Week 24
Time to clinical worsening (TTCW) evaluated in the 24-week placebo-controlled treatment period
time frame: Baseline; Week 24
Change from baseline in echocardiographic assessments of right ventricular function at Week 24
time frame: Baseline; Week 24

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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, 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 ≥ 25 mm Hg - Pulmonary vascular resistance (PVR) ≥ 400 dyne•sec/cm^5 - Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mm Hg if PVR ≥ 400 and < 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 m - 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% 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 > 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.

Additional Information

Official title A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Study of GS-4997 in Subjects With Pulmonary Arterial Hypertension
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.