Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (HYPERION)

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients

The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly called ACE-011) treatment (plus background pulmonary arterial hypertension [PAH] therapy) versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are at intermediate or high-risk of disease progression.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Other: Placebo; Drug: Sotatercept

Detailed Description

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to background PAH therapy in newly diagnosed intermediate- or high risk PAH participants.

Participants enrolled in the study will have a diagnosis within 12 months of study screening of symptomatic PAH (World Health Organization [WHO] Group 1, classified as functional class [FC] II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin- induced PAH, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects.

As of Amendment 11, this study will be closed so that all eligible participants can receive sotatercept either on the MK-7962-004 extension study (SOTERIA, NCT04796337) or by commercial access, if available. All eligible participants will complete the end of treatment visit before enrollment in the extension study or initiation of commercial product. Participants not enrolling into the extension study or initiating commercial product will complete the end of study visit.

• Study Type: Interventional
• Enrollment (Actual): 321
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5021FPQ
    • Sanatorio Allende ( Site 1908)
  • Santa Fe, Argentina, S3000EOZ
    • Hospital Provincial Dr. Jose M. Cullen ( Site 1902)
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425BNG
      • Cardiologia Palermo ( Site 1911)
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • Centro Medico Dra De Salvo ( Site 1904)
    • Pilar, Buenos Aires, Argentina, B1629ODT
      • Hospital Universitario Austral ( Site 1901)
    • Quilmes, Buenos Aires, Argentina, 1878
      • Instituto de Investigaciones Clinicas Quilmes ( Site 1903)
    • Villa Vatteone, Buenos Aires, Argentina, B1853AIK
      • Instituto De Enfermedades Respiratorias E Investigacion Medica ( Site 1910)
  • Córdoba Province
    • Córdoba, Córdoba Province, Argentina, 5003DCE
      • Instituto Médico DAMIC ( Site 1909)
    • Río Cuarto, Córdoba Province, Argentina, X5800AEV
      • Instituto Médico Río Cuarto ( Site 1907)
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2002
      • Hospital Provincial del Centenario ( Site 1912)
    • Rosario, Santa Fe Province, Argentina, S2000DSR
      • Instituto Cardiovascular de Rosario ( Site 1906)
    • Rosario, Santa Fe Province, Argentina, S2000DSV
      • Sanatorio Parque ( Site 1905)
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital ( Site 1106)
    • Newcastle, New South Wales, Australia, 2308
      • John Hunter Hospital ( Site 1101)
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital ( Site 1104)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 1108)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital ( Site 1109)
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital ( Site 1107)
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital ( Site 1103)
• Austria
  • State of Vienna
    • Vienna, State of Vienna, Austria, 1090
      • Medizinische Universitat Wien ( Site 2001)
  • Styria
    • Graz, Styria, Austria, 8036
      • Medizinische Universität Graz ( Site 2003)
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medizinische Universitat Innsbruck ( Site 2004)
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Ordensklinikum Linz GmbH Elisabethinen ( Site 2002)
• Belgium
  • Bruxelles-Capitale, Region de
    • Anderlecht, Bruxelles-Capitale, Region de, Belgium, 1070
      • Hôpital Erasme ( Site 1402)
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Gasthuisberg ( Site 1401)
• Brazil
  • São Paulo, Brazil, 05403-000
    • Instituto do Coracao - HCFMUSP ( Site 1803)
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30430-142
      • Hospital Madre Teresa ( Site 1804)
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04038-031
      • Hospital Sao Paulo ( Site 1806)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital ( Site 2101)
  • Manitoba
    • Winnepeg, Manitoba, Canada, R2H 2A6
      • St Boniface General Hospital ( Site 2106)
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • McMaster University - HSC ( Site 2105)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B Davis Jewish General Hospital ( Site 2103)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 50034
      • Centro Cardiovascular Colombiano Clínica Santa María Clínica Cardio VID ( Site 3402)
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110131
      • Fundación Neumológica Colombiana ( Site 3403)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle Del Lili ( Site 3401)
    • Cali, Valle del Cauca Department, Colombia, 760042
      • Centro Medico Imbanaco de Cali S.A ( Site 3404)
• Croatia
  • Split-Dalmatia County
    • Split, Split-Dalmatia County, Croatia, 21000
      • University Hospital Centre Split city ( Site 3901)
  • Zagreb County
    • Zagreb, Zagreb County, Croatia, 10000
      • Klinicki Bolnicki Centar Zagreb ( Site 3902)
• Czechia
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze ( Site 2201)
  • Praha 4
    • Prague, Praha 4, Czechia, 140 21
      • Institut Klinicke a Experimentalni Mediciny ( Site 2202)
• Denmark
  • Capital Region
    • København Ø, Capital Region, Denmark, 2100
      • Rigshospitalet ( Site 3802)
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Aarhus Universitetshospital, Skejby ( Site 3801)
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06001
      • Hopital Louis Pasteur ( Site 1311)
  • Auvergne
    • Lyon, Auvergne, France, 69003
      • Hôpital Louis Pradel ( Site 1317)
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67000
      • Hôpitaux Universitaires de Strasbourg ( Site 1307)
  • Brittany Region
    • Brest, Brittany Region, France, 29200
      • Hopital Cavale Blanche ( Site 1314)
  • Calvados
    • Caen, Calvados, France, 14033
      • CHU Caen Normandie ( Site 1325)
  • Doubs
    • Besançon, Doubs, France, 25000
      • CHU de Besancon ( Site 1303)
  • Gironde
    • Bordeaux, Gironde, France, 33604
      • Hopital Haut Leveque ( Site 1312)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • CHU de Toulouse - Hopital Larrey ( Site 1315)
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37000
      • C.H.U. de Tours - Hopital Bretonneau ( Site 1310)
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • Hopital Nord Laennec ( Site 1309)
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • CHU Angers ( Site 1313)
  • Meurthe-et-Moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54500
      • C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)
  • Pays de la Loire Region
    • Saint-Priest-en-Jarez, Pays de la Loire Region, France, 42270
      • Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)
  • Val-de-Marne
    • Le Kremlin-Bicêtre, Val-de-Marne, France, 94270
      • CHU - Hopital de Bicetre ( Site 1304)
  • Vienne
    • Poitiers, Vienne, France, 86000
      • CHU de Poitiers ( Site 1316)
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend ( Site 1507)
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg ( Site 1509)
  • Bavaria
    • Munich, Bavaria, Germany, 80639
      • Krankenhaus Neuwittelsbach ( Site 1510)
    • Regensburg, Bavaria, Germany, 93053
      • Universitaetsklinik Regensburg ( Site 1503)
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover ( Site 1505)
  • North Rhine-Westphalia
    • Bad Oeynhausen, North Rhine-Westphalia, Germany, 35392
      • Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Uniklinik Köln ( Site 1511)
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätsklinikum des Saarlandes ( Site 1513)
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus ( Site 1501)
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig ( Site 1508)
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Universitaetsklinik und Poliklinik Halle/Saale ( Site 1502)
• Greece
  • Thessaloniki, Greece, 546 36
    • AHEPA University General Hospital of Thessaloniki ( Site 3601)
  • Attica
    • Athens, Attica, Greece, 106 76
      • Evangelismos General Hospital of Athens ( Site 3605)
    • Athens, Attica, Greece, 176 74
      • Onassis Cardiac Surgery Center ( Site 3602)
    • Haidari, Attica, Greece, 124 62
      • Attikon University General Hospital of Athens ( Site 3604)
• Israel
  • Ashdod, Israel, 7747629
    • Assuta Ashdod Medical Center ( Site 1710)
  • Haifa, Israel, 3436212
    • Lady Davis Carmel Medical Center ( Site 1705)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 1711)
  • Tel Litwinsky, Israel, 52621
    • Sheba Medical Center ( Site 1701)
• Italy
  • Naples, Italy, 80131
    • Azienda Ospedaliera R. N. V. Monaldi ( Site 2407)
  • Roma, Italy, 161
    • La Sapienza-Università di Roma-Policlinico Umberto I ( Site 2402)
  • Friuli Venezia Giulia
    • Trieste, Friuli Venezia Giulia, Italy, 34149
      • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)
  • Lombardy
    • Milan, Lombardy, Italy, 20123
      • Ospedale S. Giuseppe Multimedica ( Site 2403)
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20900
      • Azienda Ospedaliera San Gerardo di Monza ( Site 2406)
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Radboud University Nijmegen Medical Centre ( Site 2605)
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University Medical Center ( Site 2603)
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • VU Medisch Centrum ( Site 2601)
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Erasmus MC ( Site 2604)
• New Zealand
  • Waikato Region
    • Hamilton, Waikato Region, New Zealand, 3204
      • Waikato District Health Board ( Site 2702)
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-202
      • Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 2801)
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-138
      • Instytut Gruzlicy i Chorob Pluc w Warszawie ( Site 2802)
• Portugal
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar E Universitário De Coimbra ( Site 3502)
  • Lisbon, Portugal, 1769-001
    • Hospital Pulido Valente ( Site 3503)
  • Setúbal District
    • Almada, Setúbal District, Portugal, 2801-951
      • Hospital Garcia de Orta ( Site 3501)
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia ( Site 2901)
  • Juznobacki Okrug
    • Kamenitz, Juznobacki Okrug, Serbia, 21204
      • Institute for pulmonary diseases of Vojvodina ( Site 2906)
  • Nisavski Okrug
    • Niš, Nisavski Okrug, Serbia, 18000
      • University Clinical Center Nis ( Site 2904)
  • Sumadijski Okrug
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • Clinical Center Kragujevac ( Site 2905)
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital ( Site 3102)
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System - PPDS ( Site 3101)
  • Seoul, South Korea, 06591
    • The Catholic University of Korea St. Mary s Hospital ( Site 3104)
  • Incheon
    • Namdong-Gu, Incheon, South Korea, 21565
      • Gachon University Gil Medical Center ( Site 3103)
  • Kyonggi-do
    • Gwangju, Kyonggi-do, South Korea, 61469
      • Chonnam National University Hospital ( Site 3105)
  • Seoul
    • Seuol, Seoul, South Korea, 06351
      • Samsung Medical Center ( Site 3106)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall de Hebron ( Site 1605)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 1603)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 1610)
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 1608)
  • Toledo, Spain, 45004
    • Hospital Virgen de la Salud ( Site 1607)
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07120
      • Hospital Universitario de Son Espases ( Site 1611)
  • 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
  • Skåne County
    • Lund, Skåne County, Sweden, 22185
      • Skanes Universitetssjukhus Lund ( Site 3203)
  • Uppsala County
    • Uppsala, Uppsala County, Sweden, 751 85
      • Hjart-lungmedicin och klinisk fysiologi ( Site 3204)
  • Västerbotten County
    • Umeå, Västerbotten County, Sweden, 90185
      • Norrlands Universitetssjukhus ( Site 3205)
• Switzerland
  • Zurich, Switzerland, 8091
    • UniversitätsSpital Zürich ( Site 3301)
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital ( Site 3702)
  • Taichung, Taiwan, 40447
    • China Medical University Hospital ( Site 3701)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 3703)
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital ( Site 1205)
  • Cambridgeshire
    • Cambrigge, Cambridgeshire, United Kingdom, CB23 0AY
      • Papworth Hospital NHS Foundation Trust ( Site 1208)
  • Derbyshire
    • Sheffield, Derbyshire, United Kingdom, S10 2JF
      • Sheffield Teaching Hospital NHS Foundation Trust ( Site 1207)
  • 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 6HP
      • Royal Brompton Hospital ( Site 1206)
    • London, London, City of, United Kingdom, W12 OHS
      • Imperial College Healthcare NHS Trust ( Site 1203)
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Arizona Pulmonary Specialists ( Site 1010)
    • Tucson, Arizona, United States, 85724
      • University of Arizona ( Site 1006)
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego ( Site 1002)
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center ( Site 1068)
    • Orange, California, United States, 92868
      • University of California Irvine ( Site 1086)
    • Santa Barbara, California, United States, 93105-5316
      • Santa Barbara Pulmonary Associates ( Site 1060)
    • Sherman Oaks, California, United States, 95817
      • University of California Davis Medical Center ( Site 1064)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital ( Site 1013)
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Medical Group Advanced Lung Disease ( Site 1058)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics ( Site 1050)
  • Maryland
    • Baltimore, Maryland, United States, 21287-0005
      • Johns Hopkins Hospital ( Site 1036)
  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1526
      • Tufts Medical Center - PPDS ( Site 1014)
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center ( Site 1012)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan ( Site 1011)
  • Missouri
    • Kansas City, Missouri, United States, 66160
      • University of Kansas Medical Center ( Site 1020)
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 1022)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico, Health Sciences Center ( Site 1048)
  • New York
    • New York, New York, United States, 10016-9196
      • NYU Langone Health ( Site 1052)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill ( Site 1042)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati ( Site 1035)
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation Taussig Cancer Center ( Site 1065)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-4421
      • Nazih Zuhdi Transplantation Institute ( Site 1084)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University ( Site 1054)
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Medical University of South Carolina ( Site 1003)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center ( Site 1027)
  • Texas
    • Dallas, Texas, United States, 78701
      • University of Texas Southwestern Medical Center ( Site 1038)
  • Utah
    • Salt Lake City, Utah, United States, 84132-0001
      • University of Utah ( Site 1049)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Inclusion criteria include but are not limited to:

• Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum pulmonary vascular resistance (PVR) of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO 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 World Health Organization (WHO) Functional Class (FC) II or III
• Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or above)
• Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening
• Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)

• Females of childbearing potential must meet the following criteria:

  • Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she 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 highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed to use the same highly effective contraception in combination with a barrier method 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 meet the following criteria:

  • 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

Exclusion Criteria:

Exclusion Criteria include but are not limited to:

• Diagnosis of pulmonary hypertension (PH) 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, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis
• Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest
• Baseline systolic BP < 90 mmHg at screening
• Pregnant or breastfeeding women

• Any of the following clinical laboratory values at the Screening Visit:

  • Estimated glomerular filtration rate < 30 mL/min/1.73 m^2 (as defined by The Modification of Diet in Renal Disease [MDRD] equation)
  • Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels > 3 × ULN
  • Platelet count < 50,000/mm^3 (< 50.0 × 10^9 /L)
• Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented informed consent
• Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
• History of pneumonectomy
• Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit
• Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
• 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)
• Untreated more than mild obstructive sleep apnea
• History of known pericardial constriction
• History of restrictive or congestive cardiomyopathy
• History of atrial septostomy within 180 days prior to the Screening Visit
• Electrocardiogram with Fridericia's corrected QT interval > 500 ms during the Screening Period
• Personal or family history of long QT syndrome or sudden cardiac death
• Left ventricular ejection fraction < 50% on historical echocardiogram (ECHO) 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
• 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, and vasopressin) within 30 days prior to the Screening Visit
• Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotatercept plus background PAH therapy; Participants received sotatercept at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy.	Drug: Sotatercept; SC injection; Other Names: ACE-011; MK-7962
Placebo Comparator: Placebo plus background therapy; Participants received placebo SC every 21 days plus background PAH therapy.	Other: Placebo; Placebo-matched SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Clinical Worsening	Time to clinical worsening (TTCW) is defined as time from randomization to the first confirmed morbidity event or death. Clinical worsening events are defined as all-cause death, non-planned PAH-related hospitalization of ≥ 24 hours in duration, atrial septostomy, lung transplant, and/or deterioration in performance in 6-minute walk test from baseline combined with one of the following conditions: worsening of WHO FC from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral. All events were adjudicated by a blinded, independent committee of clinical experts. The median TTCW is presented.	Up to ~35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving the Multicomponent Improvement Endpoint of 6-Minute Walk Distance (6MWD), N-terminal Prohormone B-type Natriuretic Peptide (NT-ProBNP) WHO FC	The multicomponent improvement outcome measure is determined by the percentage of participants achieving all of the following at Week 24 relative to baseline: Improvement in 6MWD (increase ≥30 m); Improvement or maintenance/achievement of NT-proBNP (decrease in NT-proBNP ≥30%) or maintenance/achievement of NT-proBNP level <300 ng/L; Improvement in WHO FC or maintenance of WHO FC II (indicated by maintaining the same WHO FC or a lower WHO FC by Week 24 relative to baseline) The percentage of participants achieving the multicomponent improvement endpoint is presented.	Baseline and Week 24
Percentage of Participants Who Achieved a Low Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 Risk Score	REVEAL Lite 2.0 risk scoring is used to guide PAH treatment decisions. Total score uses 6 variables with each assessed based on contribution to mortality risk. Variables and sub-score ranges: estimated glomerular filtration rate [eGFR] (0, +1), WHO FC (-1, 0, +1, +2), SBP (0, +1), heart rate (0, +1), 6MWD (-2, -1, 0, +1), and NT-proBNP (-2, 0, +2). Sub-scores are added to a base score of +6 and a total score of 1 to 14 is obtained (≤5=low risk; 6,7=intermediate risk; ≥8=high risk). A higher score = higher risk. Per SAP, participants who did not have a REVEAL risk score at Week 24 were considered as non-responders and multiple imputation was not conducted for this endpoint. Comparisons between this analysis reporting non-imputed data should not be made to other REVEAL analyses which included imputation of missing Week 24 data. The percentage of participants who achieved a low REVEAL Lite 2.0 score at Week 24 is reported.	Baseline and Week 24
Percentage of Participants Who Maintain or Achieve a Low Simplified French Risk Score	The simplified French Risk Score uses WHO FC, 6MWD, and NT-proBNP to determine the total risk score. A low risk score can be defined as attaining or maintaining all three low-risk criteria: WHO FC I or II, 6MWD > 440m, and NT-proBNP < 300 ng/L. The percentage of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French Risk score calculator is presented.	Baseline and Week 24
Median Change From Baseline in NT-proBNP Levels at Week 24	NT-proBNP is a circulating biomarker that reflects myocardial stretch and is an established biomarker used to determine the ventricular dysfunction in participants with PAH. NT-proBNP was measured at Day 1 (baseline) and at Week 24. The median change from baseline in NT-proBNP at Week 24 is presented.	Baseline and Week 24
Percentage of Participants Who Improve in WHO FC or Maintain WHO FC II at 24 Weeks From Baseline	The severity of an individual's PAH symptoms was graded using the WHO FC system. WHO functional classification for PAH range 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). The change from baseline in WHO FC is classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC. The percentage of participants who improve in WHO FC or maintain WHO FC II at 24 Weeks from Baseline is presented.	Baseline and Week 24
Median Change From Baseline in Six-Minute Walk Distance (6MWD)	The 6-minute walk distance (6MWD) was measured using the 6-Minute Walk Test (6MWT). The 6MWT measures the distance covered in 6 minutes and is intended to measure changes in functional exercise capacity. Each participant's 6MWD was measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicated improvement in functional exercise capacity. Median change from baseline in 6MWD at Week 24 is reported.	Baseline and Week 24
Overall Survival (OS)	Overall survival is defined as the time from randomization to date of death due to any cause. OS is presented.	Up to ~35 Months
Mean Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT)®	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. Mean change from baseline in responses in physical symptoms of the PAH-SYMPACT questionnaire at Week 24 is reported.	Baseline and Week 24
Mean Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®	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. Mean change from baseline in cardiopulmonary symptoms of the PAH-SYMPACT questionnaire at Week 24 is reported.	Baseline and Week 24
Mean Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT®	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. Mean change from baseline in responses in the Cognitive/Emotional Impacts Domain Score of the PAH-SYMPACT questionnaire at Week 24 is reported.	Baseline and Week 24
Percentage of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does 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 is considered related to the study drug. The percentage of participants who experienced an AE are presented.	Up to ~35 Months
Percentage of Participants Who Discontinued Study Treatment Due to AEs	An AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does 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 is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE are presented.	Up to ~35 months
Number of Participants Who Had Anti-drug Antibodies (ADAs) to Sotatercept	Blood samples collected at designated timepoints were used to determine the ADA response to sotatercept. The number of participants who had ADAs to sotatercept over time is presented.	Up to ~35 Months

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

• McLaughlin VV, Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, Preston IR, Souza R, Waxman AB, Kopec G, Meyer G, Olsson KM, Fu W, Shi Y, Miller B, Kim SS, Mackenzie HS, Brambatti M, Patel MJ, Koglin J, Cornell AG, Humbert M; HYPERION Trial Investigators. Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis. N Engl J Med. 2025 Oct 23;393(16):1599-1611. doi: 10.1056/NEJMoa2508170. Epub 2025 Sep 30.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Actual): April 3, 2025
• Study Completion (Actual): April 3, 2025

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Pulmonary; Sotatercept
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; ACE-011
• Other Study ID Numbers: 7962-005; A011-13 (Other Identifier: Acceleronpharma); MK-7962-005 (Other Identifier: MSD); 2021-000199-12 (EudraCT Number); 2023-509139-16-00 (Registry Identifier: EU CT); U1111-1309-6312 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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
• product manufactured in and exported from the U.S.: No