PAH Exercise Study

Eligibility Criteria

• * Age ≥ 18 years
• * Documented diagnostic right heart catheterization (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 CTD, PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair
• * Symptomatic PH classified as WHO FC II or III
• * Baseline RHC performed during the Screening Period documenting a minimum PVR of ≥ 5 WU and a pulmonary capillary wedge (PCWP) or left ventricular end-diastolic pressure of ≤ 15 mmHg
• * Receiving stable background therapy for PAH for \>90 days and will continue receiving throughout trial. Background treatments may consist of monotherapy, double therapy, or triple therapy with currently available medications for PAH.
• * Initiation of Sotatercept is clinically indicated
• * Willing and able to participate in a remotely-monitored home exercise program for 24 weeks
• * Ability to adhere to study visit schedule and understand and comply with all protocol requirements
• * Ability to understand and provide written informed consent
• * 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 and pulmonary veno-occlusive disease
• * Hemoglobin at screening above gender-specific ULN
• * Baseline platelet count \< 50,000/mm3 (\< 50.0 × 109/L) at screening
• * Uncontrolled systemic hypertension as evidenced by sitting systolic BP \> 160 mmHg or sitting diastolic BP \> 100 mmHg during screening visit after a period of rest; Baseline systolic BP \< 90 mmHg at screening
• * Pregnant or breastfeeding females
• * Clinical laboratory liver and kidney function tests outside of normal range
• * Currently enrolled in or have completed any other investigational product study within 30 days for small-molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
• * Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536) or known allergic reaction to either one
• * History of full pneumonectomy
• * Initiation of a structured exercise program within 90 days prior or planned initiation during the study
• * 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 (Child-Pugh Class A-C).
• * Cardiac related history: History of restrictive, constrictive, or congestive cardiomyopathy; History of atrial septostomy within 180 days prior to the screening visit; ECG with Fridericia's corrected QT interval (QTcF) \> 500 ms during the Screening Period; Personal or family history of long QT syndrome (LQTS) or sudden cardiac death; Left ventricular ejection fraction (LVEF) \< 45% on historical ECHO within 12 months prior to the screening visit; Any symptomatic coronary disease events (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months prior to the screening visit. Note: Anginal pain can be ignored as an exclusion criterion if coronary angiography shows no obstructions
• * Cerebrovascular accident within 3 months prior to the screening visit
• * Acutely decompensated heart failure within 14 days prior to the screening visit, as per investigator assessment
• * Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
• * Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit