Ensayos clínicos

Inclusion Criteria:

- Documented diagnostic right heart catheterization prior to screening confirming the
diagnosis of World Health Organization (WHO) pulmonary arterial hypertension (PAH)
Group 1 in any of the following subtypes:

- Idiopathic PAH;

- Heritable PAH;

- Drug/toxin-induced PAH;

- PAH associated with connective tissue diseases (CTD);

- PAH associated with simple, congenital systemic to pulmonary shunts at least 1
year following repair;

- Symptomatic PAH classified as WHO functional class (FC) III or IV.

- Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 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 pulmonary
vascular resistance (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 PAH 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 < 50,000/mm^3 (< 50.0 x 10^9/L) at screening.

- Baseline systolic blood pressure < 85 mmHg at screening.

- Pregnant or breastfeeding women.

- Serum alanine aminotransferase or aspartate aminotransferase levels or total bilirubin
> 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 accident within 3 months prior to the screening visit.

- Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular
disease.

- Currently on dialysis or anticipated need for dialysis within the next 12 months.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/3/22. Questions regarding updates should be directed to the study team contact.