A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging

Study Overview
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Brief Summary
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The purpose of the study is to assess the effects of selexipag on right ventricular (RV) function in participants with Pulmonary arterial hypertension (PAH).

Official Title
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A Prospective, Multicenter, Single-Arm, Open-Label, Phase 4 Study of the Effects of Selexipag on Right Ventricular Remodeling in Pulmonary Arterial Hypertension Assessed by Cardiac Magnetic Resonance Imaging

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: JNJ-67896049


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: World health organization functional class (WHO FC) II or III. Enrollment will be stratified by WHO FC II or III. Proportion of participants with WHO FC II and WHO FC III are expected to be approximately 40 percent (%) and 60%, respectively Pulmonary arterial hypertension (PAH) etiology belonging to one of the following groups according to 6th world symposium of pulmonary hypertension (WSPH) classification: a) Idiopathic PAH, b) Heritable PAH, c) Drugs or toxins induced d) PAH associated with connective tissue disease, e) PAH associated with congenital heart disease, with simple systemic-to-pulmonary shunt at least 1 year after surgical repair Patients already receiving PAH-specific oral mono or dual therapy (that is, phosphodiesterase type 5 inhibitors [PDE-5i] or soluble guanylate cyclase stimulators [sGCs] and/or endothelin receptor antagonist [ERA]) or patients who are not candidates for these therapies N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) greater than or equal to (>=) 300 nanograms per liter (ng/L) (greater than or equal to [>=] 300 picograms per milliliter [pg/mL]; >=35.5 picomoles per liter [pmol/L]) at screening Women of childbearing potential must meet the following criteria: a) Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, b) Agree to use acceptable methods of contraception from Day 1 to at least 30 days after study intervention discontinuation, c) If only using hormonal contraception, have used it for at least 1 month (30 days) before Day 1, and d) Agree to perform monthly pregnancy tests to at least 30 days after study intervention discontinuation 6-minute walking distance (6MWD) >=150 meter (m) during screening period Exclusion Criteria: Prior use of Prostacyclin (IP)-receptor agonist, prostacyclin, or prostacyclin analog. Use of such treatments for vasoreactivity testing is not exclusionary; intermittent use of such treatments for digital ulcers or Raynaud's phenomenon is not exclusionary if stopped > 6 months (180 days) prior to Day 1 Treatment with strong inhibitors of CYP2C8 (example, gemfibrozil) within 4 weeks (28 days) prior to Day 1 Treatment with another investigational drug planned or taken within 12 weeks (84 days) prior to Day 1 Severe coronary heart disease or unstable angina Cerebrovascular events (example, transient ischemic attack, stroke) within 3 months (90 days) prior to Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-67896049<br>Participants will receive JNJ-67896049 tablets at a starting dose of 200 mcg on Day 1. Dose will be up-titrated from Day 1 to the end of Week 12 (Day 84) to determine individual maintenance dose (IMD). Then, participants will receive JNJ-67896049 tablets at their IMD from Week 13 to Week 52. | Drug: JNJ-67896049<br>* Participants will receive tablets at a starting dose of 200 mcg on Day 1. Dose will be up-titrated from Day 1 to the end of Week 12 (Day 84) to determine individual maintenance dose (IMD). Then, participants will receive JNJ-67896049 tablets at their IMD from Week 13 to Week 52.<br>* Other names: Selexipag;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Change from baseline to week 26 in RVSV in participants will be assessed by pulmonary artery flow MRI. | Baseline and week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 26 in RV End-Diastolic Volume (RVEDV) Assessed by MRI | Change from baseline to week 26 in RVEDV will be assessed by MRI. | Baseline and week 26 | 
| Change from Baseline to Week 26 in RV End-Systolic Volume (RVESV) Assessed by MRI | Change from baseline to week 26 in RVESV will be assessed by MRI. | Baseline and week 26 | 
| Change from Baseline to Week 26 in RV Ejection Fraction (RVEF) Assessed by MRI | Change from baseline to week 26 in RVEF will be assessed by MRI. | Baseline and week 26 | 
| Change from Baseline to Week 26 in RV Mass Assessed by MRI | Change from baseline to week 26 in RV mass will be assessed by MRI. | Baseline and week 26 | 
| Change from Baseline to Week 26 RV Global Longitudinal Strain (RVGLS) Assessed by MRI | Change from baseline to week 26 RVGLS will be assessed by MRI. | Baseline and week 26 | 
| Change of Baseline to Week 26 in World Health Organization Functional Class (WHO FC) | Change of baseline to week 26 in WHO FC in participants will be assessed. | Baseline and week 26 | 
| Change form Baseline to Week 26 in N-Terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Change from baseline to week 26 NT-proBNP in participants will be assessed. | Baseline and week 26 | 
| Change from Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Change from baseline to week 26 in 6MWD in participants will be assessed. | Baseline and week 26 | 
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAE is any AE from first dose up to 3 days after end of study intervention. | Up to 56 weeks | 
| Number of Participants with Serious Adverse Events (SAEs) | A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to 60 weeks | 
| Number of Participants with AEs Leading to Premature Discontinuation of Selexipag | Number of participants with AEs leading to premature discontinuation of study drug Selexipag will be reported. | Up to 52 weeks | 
| Number of Participants with AEs of Special Interest | Number of participants with AEs of special interest will be reported. | Up to 60 weeks | 
| Number of Participants with Treatment-Emergent Marked Laboratory Abnormalities | Number of participants with treatment-emergent marked laboratory abnormalities will be reported. | Up to 56 weeks | 
| Change from Baseline to Week 26 in Number of Non-Invasive Low-Risk Criteria Variable | Change from baseline to Week 26 in number of non-invasive low-risk criteria among the following 8 variables: Absence of clinical signs of right heart failure; Absence of symptoms progression; Absence of syncope; World Health Organization functional class (WHO FC) I-II; 6-minute walking distance (6MWD) greater than (>) 440 meters (m); N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) less than (<) 300 nanogram per liters (ng/L); Right atrial (RA) area <18 centimeter square (cm^2), as determined by echocardiography (Echo) and Absence of pericardial effusion, as determined by Echo will be assessed. | Baseline to week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Right ventricle, Reverse remodeling, Magnetic resonance Imaging