Eligible participants must meet all of the following inclusion criteria to be enrolled in the study:
1. Age ≥ 18 years.
2. Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of 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.
3. Symptomatic PAH classified as WHO FC II or III.
4. On stable doses of ≥2 background PAH therapies for at least 60 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of the optimal dose is allowed per medical practice. Patients on 1 background PAH therapy are eligible if there is documented intolerance or contraindication to use of the other 2 classes (e.g. liver enzyme elevation while taking an ERA).
5. Females of childbearing potential must:
* Have a negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy.
* If sexually active, have used, and agree to use highly effective contraception without interruption 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.
6. 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
7. Ability to adhere to study visit schedule and understand and comply with all protocol requirements.
8. Ability to understand and provide written informed consent.
Exclusion Criteria
1. 1\. Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
2. Musculoskeletal limitation that precludes participation in cycle ergometry
3. Resting oxygen saturation \< 88%. (Note: patients on oxygen can be included in the study if they can maintain a resting saturation of ≥ 88 % after 3 minutes off oxygen).
4. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH and pulmonary veno-occlusive disease.
5. Hemoglobin (Hgb) at screening above the gender-specific upper limit of normal (ULN), per local laboratory test.
6. Baseline platelet count \< 50,000/mm3 (\< 50.0 × 109/L) in the enrollment period.
7. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \> 160 mmHg or sitting diastolic blood pressure \> 100 mmHg during a screening visit after a period of rest.
8. Baseline systolic blood pressure \< 90 mmHg at screening.
9. Pregnant or breastfeeding women.
10. Any of the following clinical laboratory values at the screening visit:
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min/m2 (as defined by the Modification of Diet in Renal Disease \[MDRD\] equation)
* Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels \> 3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome).
11. 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.
12. History of full pneumonectomy.
13. Pulmonary function test (PFT) values of forced vital capacity (FVC) \< 60% predicted and/or FEV1/FVC \< lower limit of normal at the screening visit or within 6 months prior to the screening visit.
14. Smoking history of ≥ 20 pack-years or any tobacco smoking or vaping within the previous 3 months.
15. Body mass index ≥ 40 kg/m2.
16. Planned initiation of an exercise program for cardiopulmonary rehabilitation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
17. 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).
18. History of restrictive, constrictive, or congestive cardiomyopathy.
19. History of atrial septostomy within 180 days prior to the screening visit.
20. Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) \> 500 ms during the Screening Period
21. Personal or family history of long QT syndrome (LQTS) or sudden cardiac death.
22. Left ventricular ejection fraction \< 45% on historical echocardiogram within 6 months prior to the screening visit.
23. 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.
24. Cerebrovascular accident within 3 months prior to the Screening Visit.
25. Significant mitral or aortic valve dysfunction (greater than moderate mitral regurgitation or aortic regurgitation, or greater than mild mitral stenosis or aortic stenosis).
26. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit.
27. Known hypersensitivity to sotatercept or to any ingredient in the formulation or component of the container.
