A Study of Sotatercept in Japanese Pulmonary Arterial Hypertension (PAH) Participants (MK-7962-020)

Study Overview
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Brief Summary
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This local Phase 3 study is planned to confirm the efficacy and safety in Japanese PAH participants. The primary population of this study is Japanese PAH participants with World Health Organization Functional Class (WHO FC) II or III while the study includes PAH participants with WHO FC I or IV as other populations. There are no hypotheses for this study.

Official Title
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A Phase 3 Non-randomized, Non-controlled, Open Label Clinical Study to Evaluate the Efficacy and Safety of MK-7962 (Sotatercept) add-on to Background Therapy in Japanese Participants With Pulmonary Arterial Hypertension (PAH)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Biological: Sotatercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnostic RHC at any time prior to screening confirming the diagnosis of WHO PAH Group 1 in any of the following subtypes: Idiopathic PAH Heritable PAH Drug/toxin-induced PAH PAH associated with connective tissue disease PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair PAH classified as WHO FC I or symptomatic PAH classified as WHO FC II to IV On stable doses of background PAH therapy and diuretics (if applicable) for at least 90 days prior to screening. Exclusion Criteria Diagnosis of PH WHO Groups 2, 3, 4, or 5. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH PAH associated with portal hypertension schistosomiasis-associated PAH PAH with features of significant venous/capillary pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH) involvement Is on the waiting list for lung transplant Pregnant or breastfeeding women. History of full or partial pneumonectomy. Pulmonary function test (PFT) values of forced vital capacity (FVC) < 60% predicted at the screening visit or within 6 months prior to the screening visit. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the screening visit or planned initiation during the study. History of more than mild obstructive sleep apnea that is untreated. Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment. History of restrictive, constrictive, or congestive cardiomyopathy. History of atrial septostomy within 180 days prior to the screening visit. Personal or family history of long QT syndrome (LQTS) or sudden cardiac death. Left ventricular ejection fraction (LVEF) < 45% on historical ECHO within 6 months prior to the screening visit. Any symptomatic coronary disease events within 6 months prior to the screening visit. Cerebrovascular accident within 3 months prior to the screening visit. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, mitral stenosis and more than mild aortic valve stenosis. Prior exposure to sotatercept or luspatercept or history of allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit. Currently enrolled in or have completed any other investigational product study within 30 days. Weight at the screening is over 85 kg.

Ages Eligible for Study
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Minimum Age: 18 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: Sotatercept<br>Participants on background PAH therapy will receive sotatercept subcutaneous (SC) injections at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg every 3 weeks up to 24 weeks. Thereafter, participants may choose to continue receiving the treatment until approval of sotatercept in Japan. | Biological: Sotatercept<br>* SC injection at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg every 21 days plus background PAH therapy.<br>* Other names: ACE-011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Pulmonary Vascular Resistance (PVR) from Baseline at Week 24 | PVR is the resistance against blood flow from the pulmonary artery to the left atrium. PVR is measured in dyn∙sec/cm^5 by right heart catheterization (RHC). RHC will be performed during the screening period (baseline) and Week 24. The change in PVR from baseline at Week 24 will be presented. | Baseline and Week 24 | 
| Number of Participants experiencing Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported. | Up to  24 weeks | 
| Number of Participants who Discontinue Study Intervention due to AEs | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported. | Up to  24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Six-minute walk distance (6MWD) at Week 24 | The distance walked in meters in 6 minutes will be measured during the screening period (baseline) and at Week 24. The change from baseline in 6MWD at Week 24 will be presented. | Baseline and Week 24 | 
| Proportion of participants with improvement in WHO FC or maintenance of WHO FC II (in participants with WHO FC II at baseline)/WHO FC I (in participants with WHO FC I at baseline) at Week 24 | Participants will have their pulmonary hypertension measured and classified during the screening period (baseline) and Week 24 as one of four categories of the WHO FC assessment ranging from I = no symptoms of pulmonary arterial hypertension with exercise or at rest to IV = symptoms at rest and severe symptoms with any activity. The proportion of participants with improvement or maintenance in WHO FC at Week 24 will be presented. | Baseline and Week 24 | 
| Change from baseline in N-terminal proB-type natriuretic peptide (NT-proBNP) at Week 24 | NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. NT-proBNP will be measured at Day 1 (baseline) and at Week 24. The change from baseline in NT-proBNP at Week 24 will be presented. | Baseline and Week 24 |