A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR)

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Biological: Sotatercept; Drug: Background PAH Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Santa Fe, Argentina, S2732XAA
    • Hospital Provincial Dr. Jose M. Cullen ( Site 1902)
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, B1629ODT
      • Hospital Universitario Austral ( Site 1901)
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Instituto de Investigaciones Clinicas Quilmes ( Site 1903)
  • Caba
    • Ciudad Autonoma de Buenos Aires, Caba, Argentina, C1426ABP
      • Centro Medico Dra De Salvo ( Site 1904)
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Sanatorio Parque ( Site 1905)
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital ( Site 1106)
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincents Hospital Sydney ( Site 1102)
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital ( Site 1101)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 1105)
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital ( Site 1104)
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital ( Site 1110)
• Belgium
  • Bruxelles-Capitale, Region De
    • Brussels, Bruxelles-Capitale, Region De, Belgium, 1070
      • Hôpital Erasme ( Site 1402)
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • U.Z.-Gasthuisberg ( Site 1401)
• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Instituto do Coracao - HC FMUSP ( Site 1803)
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre ( Site 1805)
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89030-101
      • Hospital Dia do Pulmao ( Site 1802)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • University of Alberta Hospital ( Site 2101)
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute ( Site 2104)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 2103)
• Czechia
  • Olomoucky Kraj
    • Olomouc, Olomoucky Kraj, Czechia, 779 00
      • Fakultni Nemocnice Olomouc ( Site 2203)
  • Praha 4
    • Prague, Praha 4, Czechia, 140 21
      • Institut Klinicke a Experimentalni Mediciny ( Site 2202)
  • Praha, Hlavni Mesto
    • Praha, Praha, Hlavni Mesto, Czechia, 128 08
      • Vseobecna fakultni nemocnice v Praze ( Site 2201_
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06002
      • Hopital Pasteur (Site 1311)
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67000
      • Hopitaux Universitaires de Strasbourg ( Site 1307)
  • Finistere
    • Brest, Finistere, France, 29609
      • CHRU Brest - Hopital Cavale Blanche (Site 1314)
  • Gironde
    • Pessac, Gironde, France, 33604
      • Groupe Hospitalier Sud ( Site 1312)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • CHU de Toulouse - Hopital Larrey ( Site 1315)
  • Herault
    • Montpellier, Herault, France, 34090
      • Hopital Arnaud de Villeneuve ( Site 1301)
  • Isere
    • Grenoble, Isere, France, 38043
      • CHU de Grenoble - Hopital Michallon ( Site 1303)
  • Loire
    • Saint-Priest-en-Jarez, Loire, France, 42055
      • Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • CHU Nantes - Hopital Laennec (Site 1309)
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49100
      • CHU Angers (Site 1313)
  • Meurthe-et-Moselle
    • Vandoeuvre Les Nancy, Meurthe-et-Moselle, France, 54500
      • C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille ( Site 1306)
  • Val-de-Marne
    • Le Kremlin Bicetre, Val-de-Marne, France, 94270
      • Centre Hospitalier Universitaire de Bicetre ( Site 1304)
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend ( Site 1507)
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH (Site 1509)
  • Bayern
    • Muenchen, Bayern, Germany, 80639
      • Krankenhaus Neuwittelsbach (Site 1510)
    • Regensburg, Bayern, Germany, 93053
      • Universitaetsklinik Regensburg (Site 1503)
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover (Site 1505)
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Uniklinik Köln, Institut für Kliniche Chemie ( Site 1511)
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus der TU Dresden (Site 1501)
  • Sachsen-Anhalt
    • Halle (Saale), Sachsen-Anhalt, Germany, 06120
      • Universitätsklinikum Halle (Site 1502)
• Israel
  • Haifa, Israel, 34362
    • Lady Davis Carmel Medical Center (Site 1705)
  • Kefar Saba, Israel, 4428164
    • Meir Medical Center (Site 1707)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center (Site 1703)
  • Tel Hashomer, Israel, 5265601
    • Sheba Medical Center (Site 1701)
• Italy
  • Roma, Italy, 00161
    • Universita "La Sapienza" Policlinico Umberto I (Site 2402)
• Korea, Republic of
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center (Site 3103)
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital (Site 3102)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System - PPDS (Site 3101)
• Mexico
  • Huixquilucan, Mexico, 52763
    • Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas (Site 2501)
  • Coahuila
    • Torreon, Coahuila, Mexico, 27000
      • CIMAB SA de CV (Site 2502)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64718
      • Unidad de Investigacion Clinica en Medicina, S.C. (Site 2505)
• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University Medical Center (Site 2603)
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • VU Medisch Centrum (Site 2601)
• New Zealand
  • Auckland, New Zealand, 1051
    • Greenlane Clinical Centre (Site 2703)
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • University of Otago, Wellington (Site 2701)
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
      • Waikato District Health Board (Site 2702)
• Poland
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-202
      • Krakowski Szpital Specjalistyczny im. Jana Pawla II (Site 2801)
  • Mazowieckie
    • Otwock, Mazowieckie, Poland, 05-400
      • Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina (Site 2802)
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-276
      • Uniwersytecki Szpital Kliniczny w Bialymstoku (Site 2803)
• Serbia
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • Clinical Center of Serbia (Site 2901)
    • Belgrade, Beograd, Serbia, 116550
      • Institute of Cardiovascular Diseases Dedinje (Site 2903)
  • Nisavski Okrug
    • Nis, Nisavski Okrug, Serbia, 1800
      • University Clinical Center Nis (Site 2904)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron (Site 1605)
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona (Site 1602)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal (Site 1609)
  • Madrid, Spain, 28041
    • Hospital Universitario Marques de Valdecilla (Site 1603)
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca (Site 1608)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla (Site 1601)
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro-Majadahonda (Site 1604)
• Sweden
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Akademiska Sjukhuset (Site 3204)
  • Vastra Gotalands Lan
    • Goteborg, Vastra Gotalands Lan, Sweden, 413 45
      • Sahlgrenska Universitets Sjukhuset (Site 3201)
• Switzerland
  • Zurich, Switzerland, 8091
    • Universitaetsspital Zuerich (Site 3301)
  • Geneve
    • Thonex, Geneve, Switzerland, 1226
      • Hopitaux Universitaires de Geneve HUG (Site 3302)
• United Kingdom
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G81 4DY
      • Golden Jubilee National Hospital (Site 1204)
  • London, City Of
    • London, London, City Of, United Kingdom, NW3 2QG
      • Royal Free London NHS Foundation Trust (Site 1202)
    • London, London, City Of, United Kingdom, SW3 6NP
      • Royal Brompton Hospital (Site 1206)
    • London, London, City Of, United Kingdom, W12 0HS
      • Imperial College Healthcare NHS Trust (Site 1203)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists (Site 1010)
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates, PA (Site 1008)
    • Tucson, Arizona, United States, 85724
      • University of Arizona (Site 1006)
  • California
    • San Diego, California, United States, 92037
      • University of California San Diego Medical Center (Site 1002)
    • Sherman Oaks, California, United States, 95817
      • University of California - Davis Medical Center (Site 1064)
    • Stanford, California, United States, 94305
      • Stanford University Medical Center (Site 1024)
    • Torrance, California, United States, 90502
      • Harbor UCLA Medical Center (Site 1028)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital (Site 1013)
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University Medical Faculty Associates (Site 1025)
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Mayo Clinic Jacksonville (Site 1045)
    • Tampa, Florida, United States, 33606
      • University of South Florida (Site 1043)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic (Site 1030)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists (Site 1066)
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center - PPDS (Site 1012)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital (Site 1014)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5936
      • University of Michigan (Site 1011)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota (Site 1062)
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic (Site 1023)
  • Missouri
    • Kansas City, Missouri, United States, 66160-7232
      • University of Kansas Medical Center (Site 1020)
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine (Site 1022)
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Nebraska Medical Center (Site 1053)
  • Nevada
    • Reno, Nevada, United States, 89502-1262
      • Renown Institute for Heart & Vascular Health (Site 1055)
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital (Site 1046)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center (Site 1026)
  • Ohio
    • Cincinnati, Ohio, United States, 45219-2316
      • University of Cincinnati Medical Center (Site 1035)
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital (Site 1001)
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center (Site 1005)
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center (Site 1032)
  • Oregon
    • Portland, Oregon, United States, 97232
      • Oregon Health and Science University (Site 1054)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania (Site 1047)
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian. UPMC Presbyterian Hospital (Site 1059)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital (Site 1033)
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Medical University of South Carolina - PPDS (Site 1003)
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • Statcare Pulmonary Consultants - Knoxville (Site 1031)
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (Site 1027)
  • Texas
    • Houston, Texas, United States, 77030
      • CHI St. Luke's Health Baylor College of Medicine Medical Center (Site 1044)
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital (Site 1009)
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah - PPDS (Site 1049)
  • Washington
    • Seattle, Washington, United States, 98195-0001
      • University of Washington Medical Center - Montlake (Site 1067)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus background PAH therapy; Placebo administered (SC) every 21 days plus background PAH therapy	Drug: Placebo; Placebo administered subcutaneously (SC) every 21 days plus background PAH therapy.; Drug: Background PAH Therapy; Background PAH therapy may consist of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist.
Experimental: Sotatercept plus background PAH therapy; Sotatercept at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg administered subcutaneously (SC) every 21 days plus background PAH therapy	Biological: Sotatercept; Sotatercept at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg administered subcutaneously (SC) every 21 days plus background PAH therapy.; Other Names: ACE-011; MK-7962; Drug: Background PAH Therapy; Background PAH therapy may consist of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24	The 6MWD was the distance walked in 6 minutes as a measure of functional capacity. This was assessed using the 6-minute walk test (6MWT). Per protocol, change from baseline in 6MWD at Week 24 was reported for DBPC period.	Baseline and Week 24
Number of Participants Who Experienced an Adverse Event (AE)	An AE was any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. Per protocol, the number of participants who reported an AE were reported for DBPC period.	Up to approximately 24 weeks
Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for DBPC period.	Up to approximately 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24	Multicomponent Improvement was defined as consisting of all of the following: (a) Improvement in 6MWD (increase ≥30 meters) (b) Improvement in N-terminal pro b-type natriuretic peptide (NT-proBNP; decrease in NT-proBNP ≥30%) or maintenance/achievement of NT-proBNP level <300 ng/L (c) Improvement in World Health Organization (WHO) Functional Class (FC) or maintenance of WHO FC II. Per protocol, change from baseline in the percentage of participants achieving multicomponent improvement at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24	PVR is a hemodynamic variable of pulmonary circulation and was measured by right heart catheterization (RHC). Per protocol, the change from baseline in PVR at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in NT-proBNP Levels at Week 24	NT-proBNP is a circulating biomarker that reflects myocardial stretch. Per protocol, the change from baseline in NT-proBNP level at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24	The severity of participant's pulmonary arterial hypertension (PAH) symptoms will be graded using the WHO FC system. WHO functional classification for PAH ranges from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). Participants who improve in WHO FC were classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC. Per protocol, change from baseline in the percentage of participants who improve in WHO FC at Week 24 were reported for DBPC period.	Baseline and Week 24
Time to Death or the First Occurrence of Clinical Worsening Event	Clinical Worsening events are defined as any of the following: worsening-related listing for lung and/or heart transplant; need to initiate rescue therapy with an approved background PAH therapy or the need to increase the dose of infusion prostacyclin by 10% or more; need for atrial septostomy; hospitalization for worsening of PAH (≥ 24 hours); or deterioration of PAH defined by both of the following events occurring at any time: worsened WHO FC and decrease in 6MWD by ≥15% confirmed by 2 tests at least 4 hours apart, but no more than 1 week. Per protocol, time to death or the first occurrence of clinical worsening event was reported.	Up to approximately 18 months
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	The simplified French risk scoring system was based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension (PH). In this study, the noninvasive parameters were used to determine the score. 'Low risk' was defined as attaining or maintaining all 3 low-risk criteria: WHO FC I or II, 6MWD > 440 m, and NT-proBNP <300 ng/L. Per protocol, change from baseline in percentage of participants who maintained or achieved a low risk score using the simplified French risk score calculator at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure pulmonary arterial hypertension (PAH)-related symptoms and impact of PAH on daily life. The physical impact domain consists of walking slowly on a flat surface, walking quickly on a flat surface, walking uphill, carrying things, doing light indoor household chores, washing, or dressing oneself, and needing help from others. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no physical impact to 4=severe physical impact). A higher score indicated more severe physical impact. Per protocol, change from baseline in the physical impacts domain score at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The cardiopulmonary symptoms consist of shortness of breath, fatigue, lack of energy, swelling in the ankles or legs, swelling in the stomach area, and cough. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (no symptom at all) to 4 (very severe symptoms). The mean individual symptom item score was determined for each of the 6 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items (range: 0=no cardiopulmonary symptoms to 4=severe cardiopulmonary symptoms). A higher score indicated more severe symptoms experienced. Per protocol, change from baseline in the cardiopulmonary domain score at Week 24 was reported for DBPC period.	Baseline and Week 24
Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The Cognitive/Emotional Impact domain consists of thinking clearly, feeling sad, feeling worried, and feeling frustrated. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no cognitive/emotional impact to 4=severe cognitive/emotional impact). A higher score indicated more severe cognitive/emotional impact. Per protocol, change from baseline in the cognitive/emotional impacts domain score at Week 24 was reported for DBPC period.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): December 6, 2022

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 7962-003 (Other Identifier: Merck); 2020-004142-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No