A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)

Inclusion Criteria

• Documented diagnostic right heart catheterization 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 PAH classified as WHO FC III or IV
• REVEAL Lite 2.0 risk score of ≥9
• Right heart catheterization performed during screening (or within 2 weeks prior to screening, if done at the clinical study site) documenting a minimum PVR of ≥5 Wood units and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤15 mmHg
• Clinically stable and on stable doses of maximum tolerated (per investigator's judgment) double or triple background PAH therapies for at least 30 days prior to screening
• Females of childbearing potential must:
• Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; must agree to ongoing urine or serum pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
• If sexually active with a male partner, have used, and agree to use highly effective contraception without interruption per protocol; for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment
• Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment
• Male participants must:
• Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
• Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment
• Ability to adhere to study visit schedule and understand and comply with all protocol requirements
• Ability to understand and provide written informed consent

Exclusion Criteria

• Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
• Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus-associated PAH and PAH associated with portal hypertension
• Diagnosis of pulmonary veno-occlusive diseases or pulmonary capillary hemangiomatosis or overt signs of capillary and/or venous involvement
• Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
• Baseline platelet count 3.0×ULN
• 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 or known allergic reaction to sotatercept, its excipients or luspatercept
• History of pneumonectomy
• Untreated more than mild obstructive sleep apnea
• History of known pericardial constriction
• History of restrictive or congestive cardiomyopathy
• Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) >500 ms during the screening period
• Personal or family history of long QT syndrome or sudden cardiac death
• Left ventricular ejection fraction <45% on historical echocardiogram within 1 year prior to the screening visit
• Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the screening visit
• Cerebrovascular ac