Clinical trial NCT04576988: A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare the Efficacy and Safety of Sotatercept Versus Placebo When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Hypertension
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Sponsor class: INDUSTRY
First posted: 2020-10-06
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of two treatment arms to receive either sotatercept (0.7 mg/kg) by subcutaneous administration once every 3 weeks, or placebo. All participants will be on concurrent, stable background PAH therapy. Randomization will be stratified by baseline WHO Functional Class (Class II or III) and by background PAH therapy (mono/double or triple therapy)
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to evaluate the efficacy and safety of sotatercept (MK-7962) treatment (plus background pulmonary arterial hypertension (PAH) therapy) versus placebo (plus background PAH therapy) at 24 weeks in adults with PAH. The primary hypothesis of the study is that the participants receiving sotatercept will have improved 6-minute walk distance (6MWD) at 24 weeks compared to participants receiving placebo.

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study in subjects with symptomatic PAH who present with idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug or toxin induced, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects (CHDs), and currently on background PAH therapy.

The primary efficacy endpoint of the study is exercise capacity, as measured by the 6-minute walk distance (6MWD) measured at 24 week following initiation of treatment.

Study duration will be approximately 2 years. A stratified Wilcoxon test will be used for analysis of the primary endpoint, with appropriate imputation for missing data, as detailed in the Statistical Analysis Plan. An unblinded, external, independent Data Monitoring Committee (DMC) will monitor participant safety throughout the course of the study. Participants completing this study will be eligible to receive sotatercept in a separate, open-label extension study.

Eligibility criteria: Key Inclusion Criteria:

* Age ≥ 18 years
* Documented diagnostic right heart catheterization (RHC) at any time 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 disease
  * PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
* Symptomatic PAH classified as WHO Functional Class (FC) II or III
* Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of ≥ 5 Wood units (WU) and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure of ≤ 15 mmHg.
* On stable doses of background PAH therapy and diuretics (i.e., patient-specific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice

  * Background PAH therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy with ERA, PDE5 inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists. Background PAH therapy should be stable at least 90 days prior to screening and remain stable throughout the study
  * Stable diuretic therapy is defined as no addition of a new diuretic and no switching of a pre-existent oral diuretic to parenteral administration; however, dose adjustments (up or down) in pre-existent oral diuretics are acceptable
* 6-Minute Walk Distance (6MWD) ≥ 150 and ≤ 500 m repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value)
* Females of childbearing potential must:

  * Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; she must agree to ongoing urine or serum pregnancy testing during the study and until 8 weeks after the last dose of the study drug
  * If sexually active, have used, and agree to use, highly effective contraception without interruption, 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

Key Exclusion Criteria:

* Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
* Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension. Exclusions in PAH Group I should also include schistosomiasis associate PAH and pulmonary veno occlusive disease
* Hemoglobin (Hgb) at screening above gender-specific upper limit of normal (ULN), per local laboratory test
* Baseline platelet count \< 50,000/mm\^3 (\< 50.0 x 109/L) at screening
* Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \> 160 mmHg or sitting diastolic blood pressure \> 100 mmHg during screening visit after a period of rest
* Baseline systolic blood pressure \< 90 mmHg at screening
* Pregnant or breastfeeding women
* 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
* Prior exposure to sotatercept (ACE-011) or luspatercept (ACE 536) and/or excipients or known allergic reaction to either one
* History of full pneumonectomy
* Pulmonary function test (PFT) values of forced vital capacity (FVC) \< 60% predicted at the screening visit or within 6 months prior to the screening visit. If PFT is not available, a chest CT scan showing more than mild interstitial lung disease (ILD) at the screening visit or 1 year prior to it
* Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the screening visit or planned initiation 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 more than mild obstructive sleep apnea that is untreated
* 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)
* 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
* 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
* Cerebrovascular accident within 3 months prior to the screening visit
* Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment
* Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
* Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit

Primary outcomes:
measure: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24
timeFrame: Baseline and Week 24
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 24 weeks
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 24 weeks
Secondary outcomes:
measure: Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in NT-proBNP Levels at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24
timeFrame: Baseline and Week 24
measure: Time to Death or the First Occurrence of Clinical Worsening Event
timeFrame: Up to approximately 18 months
measure: Change From Baseline in Percentage of Participants Who Maintain or Achieve a Low Risk Score Using the Simplified French Risk Score Calculator at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists (Site 1010)
state: Arizona
city: Phoenix
country: United States
facility: Pulmonary Associates, PA (Site 1008)
state: Arizona
city: Tucson
country: United States
facility: University of Arizona (Site 1006)
state: Arizona
city: San Diego
country: United States
facility: University of California San Diego Medical Center (Site 1002)
state: California
city: Sherman Oaks
country: United States
facility: University of California - Davis Medical Center (Site 1064)
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center (Site 1024)
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center (Site 1028)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital (Site 1013)
state: Colorado
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates (Site 1025)
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville (Site 1045)
state: Florida
city: Tampa
country: United States
facility: University of South Florida (Site 1043)
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic (Site 1030)
state: Georgia
city: Louisville
country: United States
facility: Norton Pulmonary Specialists (Site 1066)
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center - PPDS (Site 1012)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital (Site 1014)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan (Site 1011)
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota (Site 1062)
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic (Site 1023)
state: Minnesota
city: Kansas City
country: United States
facility: University of Kansas Medical Center (Site 1020)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine (Site 1022)
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center (Site 1053)
state: Nebraska
city: Reno
country: United States
facility: Renown Institute for Heart & Vascular Health (Site 1055)
state: Nevada
city: New York
country: United States
facility: New York Presbyterian Hospital (Site 1046)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (Site 1026)
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center (Site 1035)
state: Ohio
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital (Site 1001)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center (Site 1005)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center (Site 1032)
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University (Site 1054)
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania (Site 1047)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian. UPMC Presbyterian Hospital (Site 1059)
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital (Site 1033)
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS (Site 1003)
state: South Carolina
city: Knoxville
country: United States
facility: Statcare Pulmonary Consultants - Knoxville (Site 1031)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 1027)
state: Tennessee
city: Houston
country: United States
facility: CHI St. Luke's Health Baylor College of Medicine Medical Center (Site 1044)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital (Site 1009)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - PPDS (Site 1049)
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake (Site 1067)
state: Washington
city: Pilar
country: Argentina
facility: Hospital Universitario Austral ( Site 1901)
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes ( Site 1903)
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra De Salvo ( Site 1904)
state: Caba
city: Rosario
country: Argentina
facility: Sanatorio Parque ( Site 1905)
state: Santa Fe
city: Santa Fe
country: Argentina
facility: Hospital Provincial Dr. Jose M. Cullen ( Site 1902)
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital ( Site 1106)
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney ( Site 1102)
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital ( Site 1101)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 1105)
state: New South Wales
city: Chermside
country: Australia
facility: Prince Charles Hospital ( Site 1104)
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital ( Site 1110)
state: Victoria
city: Brussels
country: Belgium
facility: Hopital Erasme ( Site 1402)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: U.Z.-Gasthuisberg ( Site 1401)
state: Vlaams-Brabant
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Hospital Dia do Pulmao ( Site 1802)
state: Santa Catarina
city: Sao Paulo
country: Brazil
facility: Instituto do Coracao - HC FMUSP ( Site 1803)
city: Edmonton
country: Canada
facility: University Of Alberta Hospital ( Site 2101)
state: Alberta
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute ( Site 2104)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 2103)
state: Quebec
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc ( Site 2203)
state: Olomoucky Kraj
city: Prague
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny ( Site 2202)
state: Praha 4
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze ( Site 2201_
state: Praha, Hlavni Mesto
city: Nice
country: France
facility: Hopital Pasteur (Site 1311)
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg ( Site 1307)
state: Bas-Rhin
city: Brest
country: France
facility: CHRU Brest - Hopital Cavale Blanche (Site 1314)
state: Finistere
city: Pessac
country: France
facility: Groupe Hospitalier Sud ( Site 1312)
state: Gironde
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Larrey ( Site 1315)
state: Haute-Garonne
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve ( Site 1301)
state: Herault
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital Michallon ( Site 1303)
state: Isere
city: Nantes
country: France
facility: CHU Nantes - Hopital Laennec (Site 1309)
state: Loire-Atlantique
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)
state: Loire
city: Angers
country: France
facility: CHU Angers (Site 1313)
state: Maine-et-Loire
city: Vandoeuvre Les Nancy
country: France
facility: C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)
state: Meurthe-et-Moselle
city: Lille
country: France
facility: CHRU Lille ( Site 1306)
state: Nord
city: Le Kremlin Bicetre
country: France
facility: Centre Hospitalier Universitaire de Bicetre ( Site 1304)
state: Val-de-Marne
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH (Site 1509)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Krankenhaus Neuwittelsbach (Site 1510)
state: Bayern
city: Regensburg
country: Germany
facility: Universitaetsklinik Regensburg (Site 1503)
state: Bayern
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (Site 1505)
state: Niedersachsen
city: Köln
country: Germany
facility: Uniklinik Köln, Institut für Kliniche Chemie ( Site 1511)
state: Nordrhein-Westfalen
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Site 1502)
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus der TU Dresden (Site 1501)
state: Sachsen
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend ( Site 1507)
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center (Site 1705)
city: Kefar Saba
country: Israel
facility: Meir Medical Center (Site 1707)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center (Site 1703)
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center (Site 1701)
city: Roma
country: Italy
facility: Universita "La Sapienza" Policlinico Umberto I (Site 2402)
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center (Site 3103)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (Site 3102)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS (Site 3101)
city: Torreon
country: Mexico
facility: CIMAB SA de CV (Site 2502)
state: Coahuila
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina, S.C. (Site 2505)
state: Nuevo Leon
city: Huixquilucan
country: Mexico
facility: Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas (Site 2501)
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center (Site 2603)
state: Limburg
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum (Site 2601)
state: Noord-Holland
city: Christchurch
country: New Zealand
facility: University of Otago, Wellington (Site 2701)
state: Canterbury
city: Hamilton
country: New Zealand
facility: Waikato District Health Board (Site 2702)
state: Waikato
city: Auckland
country: New Zealand
facility: Greenlane Clinical Centre (Site 2703)
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II (Site 2801)
state: Malopolskie
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina (Site 2802)
state: Mazowieckie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku (Site 2803)
state: Podlaskie
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia (Site 2901)
state: Beograd
city: Belgrade
country: Serbia
facility: Institute of Cardiovascular Diseases Dedinje (Site 2903)
state: Beograd
city: Nis
country: Serbia
facility: University Clinical Center Nis (Site 2904)
state: Nisavski Okrug
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla (Site 1601)
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda (Site 1604)
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (Site 1605)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (Site 1602)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal (Site 1609)
city: Madrid
country: Spain
facility: Hospital Universitario Marques de Valdecilla (Site 1603)
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca (Site 1608)
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset (Site 3204)
state: Uppsala Lan
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitets Sjukhuset (Site 3201)
state: Vastra Gotalands Lan
city: Thonex
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG (Site 3302)
state: Geneve
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich (Site 3301)
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital (Site 1204)
state: Glasgow City
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust (Site 1202)
state: London, City Of
city: London
country: United Kingdom
facility: Royal Brompton Hospital (Site 1206)
state: London, City Of
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust (Site 1203)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6.