The objective of this study is to evaluate the effects of sotatercept treatment (plus maximum tolerated background PAH therapy) versus placebo (plus maximum tolerated background PAH therapy) on time to first event of all cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours, in participants with WHO FC III or FC IV PAH at high risk of mortality. The study targets patients with symptomatic PAH (WHO FC III or FC IV at high risk of mortality) who present with idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxininduced, post-shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defect. Up to 166 participants will be randomly assigned in a 1:1 ratio to the
2 study treatment groups (83 participants per arm). Maximum study duration for a given participant in this study will be up to approximately 49 months.

The objective of this study is to evaluate the effects of sotatercept treatment (plus background PAH therapy) verses placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are in intermediate or high risk of disease progression. The study is divided into a Screening Period (up to 4 weeks), followed by a Double-blind Placebo-controlled (DBPC) Treatment Period. When a participant experiences an event of clinical worsening, they will complete the End of Treatment (EOT) Visit and will be eligible to enroll immediately in the open-label, long-term follow-up (LTFU) study, A011-12 (SOTERIA). Up to 662 participants will be randomly assigned in a 1:1 ratio to the 2 study treatment groups (331 participants per arm).

This open-label, LTFU study will evaluate the safety, tolerability, and efficacy of sotatercept in participants with PAH previously treated with sotatercept or placebo. Participants eligible to enroll in this study will have participated in and completed the relevant study participants of the parent PAH sotatercept clinical trials. The estimated duration of the A011-12 study is up to 7 years; however, the estimated duration of enrollment for each participants is approximately 4 years. There is no formal sample size calculation for the study. The number of participants in this LTFU study is dependent upon the enrollment in the parent protocols. Approximately 700 participants are anticipated to enroll in the study.

The PHAR is a multicenter, prospective registry of newly evaluated patients at PHCCs in the United States who have either PAH or CTEPH. Baseline information will be collected at the time of initial evaluation at the PHCC (within six months of the initial outpatient PHCC visit) with follow-up data collected at approximately 6-month intervals. This study will determine how patients with PH are evaluated, tested, and treated, and will observe how well patients do. The goal of the project is to see if patients with PH are treated according to recommended guidelines and to see if there are certain factors which lead to better or worse outcomes in patients with PH. There is no intervention or study medication used and there is no limitation to how a patient is treated in this study.

The purpose of this study is to determine if the study drug, inhaled nitric oxide, when given and breathed through an investigational study device called the INOpulse, may help treat PF. Inhaled nitric oxide is a drug approved by the FDA and Health Canada for the treatment of infants who have difficulty breathing and have decreased oxygen in their blood associated with pulmonary hypertension. Inhaled nitric oxide and the INOpulse delivery device are investigational for the treatment of PF with and without pulmonary hypertension and are not currently an approved treatment. Because we do not know if this drug and device combination will treat PF, we need to compare it against a placebo (a pretend drug that has no effect on a person). To do this, we will put people taking part in this study into two groups. The groups are selected by chance, like a coin toss. Participants in one group will be given the study drug while participants in the other group will be given the pretend drug.

Subjects with Pulmonary Arterial Hypertension (PAH) will be asked to have blood drawn at their standard of care visit. Children (11 years and older) and adults are eligible. This study is voluntary. Blood samples obtained and the associated blood products and clinical/genetic data will be in the research study for a minimum of five years.