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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: JTT-251
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events |  | 28 Weeks | 
| JTT-251 trough plasma concentrations |  | 4, 12 and 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JTT-251, Pulmonary arterial hypertension, RELIEF-PAH, Six-minute walk distance (6MWD)