Clinical Research Directory

Part 1: Inclusion Criteria: * Able to provide informed consent * Age 18-80 years * PAH which is idiopathic, heritable or associated with drugs, toxins or connective tissue disease * Stable PAH therapeutic regime comprising any combination of ERA and PDE5i for at least 1 month prior to screening (unless unable to tolerate therapy) * WHO functional class III * Resting mPAP ≥20 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, pulmonary vascular resistance ≥2 Wood Units measured by right heart catheterisation at time of diagnosis * 6MWT \>50m at entry * Estimated glomerular filtration rate (eGFR)\>30 ml/min/1.73 m² at entry (Appendix C) * Inadequate treatment response (clinically determined) Exclusion Criteria: * Unable to provide informed consent * Pregnancy * Unprovoked pulmonary embolism (at any time) * Acute infection at time of screening (rescreening is permitted) * PAH due to human immunodeficiency virus, portal hypertension, schistosomiasis, congenital heart disease * Pulmonary hypertension due to left heart, lung, thromboembolic or unclear/multifactorial disease (Group II-V) * Unable to tolerate aspirin or P2Y12 inhibitor * Hypersensitivity to selexipag or riociguat * Clinically-significant renal disease (eGFR≤30 ml/min/1.73m2) * Anaemia (haemoglobin \<10 g/dl) * Left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following: aortic or mitral valve disease greater than mild aortic insufficiency; mild aortic stenosis; mild mitral stenosis; or moderate mitral regurgitation Part 2: Inclusion criteria: * Able to provide informed consent * Age 18-80 years * PAH which is idiopathic, heritable or associated with drugs, toxins or connective tissue disease * Stable PAH doses of background PAH therapy for at least 30 days prior to screening with inadequate treatment response (clinically determined) * WHO FC II or III despite treatment with diuretics * Field Walk Distance thresholds: 6MWT \>50m at entry or ISWT \>180m or equivalent ESWD * Patients of childbearing potential must: 1. Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting the study. 2. Agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of sotatercept 3. If sexually active, have used and agree to use, highly effective contraception without interruption for at least 28 days prior to starting sotatercept, during the study and for 16 weeks (112 days) after discontinuation * Patients of non-childbearing potential must: 1. Agree to use a condom, defined as a male latex condom or non-latex condom NOT made from natural (animal) membrane (e.g. polyurethane), during sexual contact with a pregnant person of childbearing potential while participating in the study, during dose interruptions and for at least 16 weeks (112 days) following discontinuation of sotatercept 2. Refrain from donating blood or sperm for the duration of the study and for 112 days after the last dose of sotatercept * Ability to adhere to study visit schedule and comply with all protocol requirements for sotatercept monitoring Exclusion criteria: * Unable to provide informed consent * Pregnancy or breast feeding * Unprovoked pulmonary embolism (at any time) * Acute infection at time of screening (rescreening is permitted) * PAH due to human immunodeficiency virus, portal hypertension, schistosomiasis, congenital heart disease * Pulmonary hypertension due to left heart, lung, thromboembolic or unclear/multifactorial disease (Group II-V) * Unable to tolerate aspirin or P2Y12 inhibitor * Any of the following clinical laboratory defined values at the screening visit. 1. Platelet count \<50 x 109/L 2. Haemoglobin above gender-specific upper limit of normal as per local laboratory test 3. eGFr \<30mL/min/m2 (as defined by MDRD equation) 4. serum ALT or AST \>3x upper limit of normal 5. total bilirubin \>1.5x upper limit of normal * 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 * Known allergic reaction to sotatercept (ACE-011) or luspatercept (ACE-536) * Left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following: aortic or mitral valve disease greater than mild aortic insufficiency; mild aortic stenosis; mild mitral stenosis; or moderate mitral regurgitation