Testing Sotatercept for pulmonary artery hypertension

Inclusion

• +Age ≥ 18 years.
• +Known hypersensitivity to sotatercept or to any ingredient in the formulation or component of the container.
• +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.
• +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).
• +to be enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more → in the study:
• +Documented diagnostic right heart catheterization (RHC) at any time prior to screeningScreeningThe checks done before joining, to see whether a study fits.Read more → 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.
• +Symptomatic PAH classified as WHO FC II or III.
• +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).
• +Male participants must:
• +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 protocolProtocolThe detailed plan a study must follow.Read more → requirements.
• +Ability to understand and provide written informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →.
• +Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +1\. Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
• +Musculoskeletal limitation that precludes participation in cycle ergometry
• +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).
• +Hemoglobin (Hgb) at screening above the gender-specific upper limit of normal (ULN), per local laboratory test.
• +BaselineBaselineYour starting measurements, taken before treatment begins.Read more → platelet count \< 50,000/mm3 (\< 50.0 × 109/L) in the enrollment period.
• +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.
• +Baseline systolic blood pressure \< 90 mmHg at screening.
• +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).
• +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.
• +History of full pneumonectomy.
• +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.
• +Body mass index ≥ 40 kg/m2.
• +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).
• +History of restrictive, constrictive, or congestive cardiomyopathy.
• +History of atrial septostomy within 180 days prior to the screening visit.
• +Electrocardiogram (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 \< 45% on historical echocardiogram within 6 months prior to the screening visit.
• +Cerebrovascular accident within 3 months prior to the Screening Visit.
• +Significant mitral or aortic valve dysfunction (greater than moderate mitral regurgitation or aortic regurgitation, or greater than mild mitral stenosis or aortic stenosis).
• +Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit.
• +Females of childbearing potential must:
• +Have a negative urine or serum pregnancy tests as verified by the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → 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.
• +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.
• +Pregnant or breastfeeding women.
• +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.
• +Smoking history of ≥ 20 pack-years or any tobacco smoking or vaping within the previous 3 months.