Study to Evaluate Efficacy and Safety of JTT-251 in Participants With Pulmonary Arterial Hypertension (RELIEF-PAH)

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of JTT-251 Administered for 24 Weeks to Participants With Pulmonary Arterial Hypertension (RELIEF-PAH)

Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-251 administered for 24 weeks in participants with pulmonary arterial hypertension (PAH)

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: JTT-251; Drug: Placebo

Detailed Description

This is a study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-251 administered for 24 weeks in participants with pulmonary arterial hypertension (PAH). Participants completing this study (RELIEF-PAH) will be eligible to enroll in an open-label extension study (RELIEF-PAH OLE) to evaluate the long-term efficacy, safety, tolerability and pharmacokinetics of JTT-251 in participants with PAH.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of PAH as classified by idiopathic, heritable, drug and toxin- induced, congenital heart disease or associated with connective tissue disease (i.e., WHO Group 1)
• Clinical diagnosis of PAH confirmed by RHC at any time prior to Visit 1
• WHO functional status of Class II-IV at Visit 1
• Two 6MWD test measurements between 100 and 450 meters with a relative difference of ≤15%. The baseline 6MWD test must be performed at Visit 2 before randomization.
• Have a qualifying RHC performed between Visit 1 and Visit 2
• On stable dose(s) of guideline-directed medical therapy for PAH (endothelin receptor antagonists, phosphodiesterase type-5 (PDE-5) inhibitors, soluble guanylate cyclase stimulators and prostacyclin pathway analogs) for at least 90 days prior to the qualifying RHC

Exclusion Criteria:

• PAH associated with portal hypertension, human immunodeficiency virus (HIV), schistosomiasis or sickle cell disease as well as participants with pulmonary parenchymal disease or thromboembolic disease
• Known significant left heart disease including: left ventricular dysfunction (i.e., left ventricular ejection fraction <35%); hemodynamically compromising, symptomatic, or severe aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation
• Pulmonary hypertension belonging to WHO groups 2 to 5
• Moderate to severe obstructive lung disease defined as forced expiratory volume in 1 second (FEV1) <55% of predicted value
• Moderate to severe restrictive lung disease defined as total lung capacity (TLC) <60% of predicted value
• Acute decompensated heart failure or hospital admission for worsening PAH symptoms within 30 days prior to the qualifying RHC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JTT-251 Dose 1; One dose of study drug by mouth daily for 24 weeks	Drug: JTT-251; Active drug tablets containing JTT-251
Experimental: JTT-251 Dose 2; One dose of study drug by mouth daily for 24 weeks	Drug: JTT-251; Active drug tablets containing JTT-251
Experimental: JTT-251 Dose 3; One dose of study drug by mouth daily for 24 weeks	Drug: JTT-251; Active drug tablets containing JTT-251
Placebo Comparator: Placebo; One dose of study drug by mouth daily for 24 weeks	Drug: Placebo; Placebo tablets matching in appearance to the active drug tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in six-minute walk distance (6MWD) compared to baseline		24 Weeks
Change in World Health Organization (WHO) functional classification compared to baseline		24 Weeks
Change in pulmonary vascular resistance (PVR) compared to baseline	Assessed by right heart catheterization (RHC)	4, 12, 24 and 28 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events	28 Weeks
JTT-251 trough plasma concentrations	4, 12 and 24 Weeks

Collaborators and Investigators

• Sponsor: Akros Pharma Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: December 26, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2019
• Last Update Submitted That Met QC Criteria: May 1, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary arterial hypertension; JTT-251; RELIEF-PAH; Six-minute walk distance (6MWD)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: AT251-G-17-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No