PAH Exercise Study

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 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