Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (HYPERION)
Pulmonary Arterial Hypertension
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary, Hypertension, Sotatercept
Eligibility Criteria
Inclusion Criteria:
Eligible participants must meet all of the following criteria to be enrolled in the study:
- Age ≥ 18 years
Documented diagnostic right heart catheterization (RHC) within 6 months of screening documenting a minimum 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 WHO FC II or III
- REVEAL Lite 2 Risk Score ≥ 6
- Diagnosis of PAH within 12 months of screening and on stable doses of a double combination of background PAH therapies and diuretics 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
- Ability to adhere to study visit schedule and understand and comply with all protocol requirements
- Ability to understand and provide written informed consent
Exclusion Criteria:
Participants will be excluded from the study if any of the following criteria are met:
- 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) > 160 mmHg or sitting diastolic BP > 100 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/m2 (as defined by MDRD equation)
- Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels > 3 × ULN
- Platelet count < 50,000/mm3 (< 50.0 × 109 /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
- 18. 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
Sites / Locations
- Arizona Pulmonary Specialists ( Site 1010)Recruiting
- University of Arizona ( Site 1006)Recruiting
- University of California San Diego ( Site 1002)Recruiting
- David Geffen School of Medicine at UCLA ( Site 1068)Recruiting
- University of California Irvine ( Site 1086)Recruiting
- Jeffrey S.Sager MD Medical Corporation ( Site 1060)Recruiting
- University of California Davis Medical Center ( Site 1064)Recruiting
- University of Colorado Hospital ( Site 1013)Recruiting
- AdventHealth Medical Group Advanced Lung Disease ( Site 1058)Recruiting
- University of Iowa Hospital and Clinics ( Site 1050)Recruiting
- Johns Hopkins Hospital ( Site 1036)Recruiting
- Tufts Medical Center ( Site 1012)Recruiting
- Brigham & Women's Hospital ( Site 1014)Recruiting
- University of Michigan ( Site 1011)Recruiting
- University of Kansas Medical Center ( Site 1020)Recruiting
- Washington University School of Medicine ( Site 1022)Recruiting
- University of New Mexico, Health Sciences Center ( Site 1048)Recruiting
- NYU Langone Health ( Site 1052)Recruiting
- University of North Carolina at Chapel Hill ( Site 1042)Recruiting
- The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)Recruiting
- University of Cincinnati Health ( Site 1035)Recruiting
- The Cleveland Clinic Foundation Taussig Cancer Center ( Site 1065)Recruiting
- Nazih Zuhdi Transplantation Institute ( Site 1084)Recruiting
- Oregon Health & Science University ( Site 1054)Recruiting
- Medical University of South Carolina ( Site 1003)Recruiting
- University of Texas Southwestern Medical Center ( Site 1038)Recruiting
- University of Utah ( Site 1049)Recruiting
- Cardiologia Palermo ( Site 1911)Recruiting
- Centro Medico Dra De Salvo ( Site 1904)Recruiting
- Hospital Universitario Austral ( Site 1901)Recruiting
- Instituto de Investigaciones Clinicas Quilmes ( Site 1903)Recruiting
- Instituto De Enfermedades Respiratorias E Investigacion Medica ( Site 1910)Recruiting
- Instituto Médico DAMIC ( Site 1909)Recruiting
- Instituto Medico Rio Cuarto ( Site 1907)Recruiting
- Hospital Provincial del Centenario ( Site 1912)Recruiting
- Instituto Cardiovascular de Rosario ( Site 1906)Recruiting
- Sanatorio Parque ( Site 1905)Recruiting
- Sanatorio Allende ( Site 1908)Recruiting
- Hospital Provincial Dr. Jose M. Cullen ( Site 1902)Recruiting
- Royal Prince Alfred Hospital ( Site 1106)Recruiting
- John Hunter Hospital ( Site 1101)Recruiting
- Prince Charles Hospital ( Site 1104)Recruiting
- Princess Alexandra Hospital ( Site 1108)Recruiting
- Royal Adelaide Hospital ( Site 1109)Recruiting
- Royal Hobart Hospital ( Site 1107)Recruiting
- Fiona Stanley Hospital ( Site 1103)Recruiting
- Ordensklinikum Linz GmbH Elisabethinen ( Site 2002)Recruiting
- Medizinische Universität Graz ( Site 2003)Recruiting
- Medizinische Universitat Innsbruck ( Site 2004)Recruiting
- Medizinische Universitat Wien ( Site 2001)Recruiting
- Hopital Erasme ( Site 1402)Recruiting
- UZ Gasthuisberg ( Site 1401)Recruiting
- Hospital Madre Teresa ( Site 1804)Recruiting
- Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)Recruiting
- Hospital Sao Paulo ( Site 1806)Recruiting
- Instituto do Coracao - HCFMUSP ( Site 1803)Recruiting
- University of Alberta Hospital ( Site 2101)Recruiting
- St Boniface General Hospital ( Site 2106)Recruiting
- St. Joseph's Healthcare Hamilton ( Site 2105)Recruiting
- Sir Mortimer B Davis Jewish General Hospital ( Site 2103)Recruiting
- Centro Cardiovascular Colombiano Clínica Santa María Clínica Cardio VID ( Site 3402)Recruiting
- Fundacion Neumologica Colombiana ( Site 3403)Recruiting
- Fundacion Valle Del Lili ( Site 3401)Recruiting
- Centro Medico Imbanaco de Cali S.A ( Site 3404)Recruiting
- University Hospital Centre Split city ( Site 3901)Recruiting
- Klinicki Bolnicki Centar Zagreb ( Site 3902)Recruiting
- Institut Klinicke a Experimentalni Mediciny ( Site 2202)Recruiting
- Vseobecna fakultni nemocnice v Praze ( Site 2201)Recruiting
- Rigshospitalet ( Site 3802)Recruiting
- Aarhus Universitetshospital, Skejby ( Site 3801)Recruiting
- Hopital Louis Pasteur ( Site 1311)Recruiting
- Hopital Louis Pradel ( Site 1317)Recruiting
- Hopitaux Universitaires de Strasbourg ( Site 1307)Recruiting
- Hopital Cavale Blanche ( Site 1314)Recruiting
- Hopital de la Cote de Nacre - Caen ( Site 1325)Recruiting
- Hopital Haut Leveque ( Site 1312)Recruiting
- CHU de Toulouse - Hopital Larrey ( Site 1315)Recruiting
- C.H.U. de Tours - Hopital Bretonneau ( Site 1310)Recruiting
- CHU de Grenoble - Hopital Michallon ( Site 1303)Recruiting
- Hopital Nord Laennec ( Site 1309)Recruiting
- Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)Recruiting
- CHU Angers ( Site 1313)Recruiting
- C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)Recruiting
- CHU - Hopital de Bicetre ( Site 1304)Recruiting
- CHRU LA MILETRIE ( Site 1316)Recruiting
- Thoraxklinik-Heidelberg gGmbH ( Site 1509)Recruiting
- Krankenhaus Neuwittelsbach ( Site 1510)Recruiting
- Universitaetsklinik Regensburg ( Site 1503)Recruiting
- Medizinische Hochschule Hannover ( Site 1505)Recruiting
- Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)Recruiting
- Uniklinik Köln ( Site 1511)Recruiting
- Universitatsklinikum des Saarlandes ( Site 1513)Recruiting
- Universitaetsklinik und Poliklinik Halle/Saale ( Site 1502)Recruiting
- Universitaetsklinikum Carl Gustav Carus ( Site 1501)Recruiting
- Universitatsklinikum Leipzig ( Site 1508)Recruiting
- DRK Kliniken Berlin Westend ( Site 1507)Recruiting
- Onassis Cardiac Surgery Center ( Site 3602)Recruiting
- Evangelismos General Hospital of Athens ( Site 3605)Recruiting
- Attikon University General Hospital of Athens ( Site 3604)Recruiting
- AHEPA University General Hospital of Thessaloniki ( Site 3601)Recruiting
- Assuta Ashdod Medical Center ( Site 1710)Recruiting
- Lady Davis Carmel Medical Center ( Site 1705)Recruiting
- Hadassah Medical Center ( Site 1711)Recruiting
- Sheba Medical Center ( Site 1701)Recruiting
- Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)Recruiting
- Ospedale S. Giuseppe Multimedica ( Site 2403)Recruiting
- Azienda Ospedaliera San Gerardo di Monza ( Site 2406)Recruiting
- Azienda Ospedaliera R. N. V. Monaldi ( Site 2407)Recruiting
- Azienda Policlinico Umberto I ( Site 2402)Recruiting
- Gachon University Gil Medical Center ( Site 3103)Recruiting
- Chonnam National University Hospital ( Site 3105)Recruiting
- Samsung Medical Center ( Site 3106)Recruiting
- Seoul National University Hospital ( Site 3102)Recruiting
- Severance Hospital Yonsei University Health System - PPDS ( Site 3101)Recruiting
- The Catholic University of Korea St. Mary s Hospital ( Site 3104)Recruiting
- Radboud University Nijmegen Medical Centre ( Site 2605)Recruiting
- Maastricht University Medical Center ( Site 2603)Recruiting
- VU Medisch Centrum ( Site 2601)Recruiting
- Erasmus MC ( Site 2604)Recruiting
- Waikato District Health Board ( Site 2702)Recruiting
- Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 2801)Recruiting
- Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)Recruiting
- Hospital Garcia de Orta ( Site 3501)Recruiting
- Centro Hospitalar E Universitário De Coimbra ( Site 3502)Recruiting
- Hospital Pulido Valente ( Site 3503)Recruiting
- Institute for pulmonary diseases of Vojvodina ( Site 2906)Recruiting
- University Clinical Center Nis ( Site 2904)Recruiting
- Clinical Center Kragujevac ( Site 2905)Recruiting
- Clinical Center of Serbia ( Site 2901)Recruiting
- Hospital Universitario Marques de Valdecilla ( Site 1601)Recruiting
- Hospital Universitario de Son Espases ( Site 1611)Recruiting
- Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)Recruiting
- Hospital Universitari Vall de Hebron ( Site 1605)Recruiting
- Hospital Universitario 12 de Octubre ( Site 1603)Recruiting
- Hospital Universitario La Paz ( Site 1610)Recruiting
- Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 1608)Recruiting
- Hospital Universitario de Toledo ( Site 1607)Recruiting
- Skanes Universitetssjukhus Lund ( Site 3203)
- Akademiska Sjukhuset [Uppsala, Sweden] ( Site 3204)Recruiting
- Norrlands Universitetssjukhus ( Site 3205)Recruiting
- UniversitätsSpital Zürich ( Site 3301)Recruiting
- Kaohsiung Veterans General Hospital ( Site 3702)Recruiting
- China Medical University Hospital ( Site 3701)Recruiting
- National Cheng Kung University Hospital ( Site 3703)Recruiting
- Papworth Hospital NHS Foundation Trust ( Site 1208)Recruiting
- Sheffield Teaching Hospital NHS Foundation Trust ( Site 1207)Recruiting
- Golden Jubilee National Hospital ( Site 1204)Recruiting
- Royal Free London NHS Foundation Trust ( Site 1202)Recruiting
- Royal Brompton Hospital ( Site 1206)Recruiting
- Imperial College Healthcare NHS Trust ( Site 1203)Recruiting
- Freeman Hospital ( Site 1205)Recruiting
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Placebo plus background PAH therapy
Sotatercept plus background PAH therapy
Administered subcutaneously (SC) every 21 days plus background PAH therapy
Administered 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