A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH) (ZENITH)
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:
Documented diagnostic right heart catheterization prior to screening confirming the diagnosis of World Health Organization (WHO) pulmonary arterial hypertension (PAH) Group 1 in any of the following subtypes:
- Idiopathic PAH
- Heritable PAH
- Drug/toxin-induced PAH
- PAH associated with connective tissue diseases (CTD)
- PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
- Symptomatic PAH classified as WHO functional class (FC) III or IV
- Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 risk score of ≥9
- Right heart catheterization performed during screening (or within 2 weeks prior to screening, if done at the clinical study site) documenting a minimum pulmonary vascular resistance (PVR) of ≥5 Wood units and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤15 mmHg
- Clinically stable and on stable doses of maximum tolerated (per investigator's judgment) double or triple background PAH therapies for at least 30 days prior to screening
Females of childbearing potential must:
- Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; must agree to ongoing urine or serum pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
- If sexually active with a male partner, have used, and agree to use highly effective contraception without interruption per protocol; for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment
- Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment
Male participants must:
- Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
- Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment
- Ability to adhere to study visit schedule and understand and comply with all protocol requirements
- Ability to understand and provide written informed consent
Exclusion Criteria:
- Diagnosis of PAH WHO Groups 2, 3, 4, or 5
- Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus-associated PAH and PAH associated with portal hypertension
- Diagnosis of pulmonary veno-occlusive diseases or pulmonary capillary hemangiomatosis or overt signs of capillary and/or venous involvement
- Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
- Baseline platelet count <50,000/mm3 (<50.0 x 109/L) at screening
- Baseline systolic blood pressure <85 mmHg at screening
- Pregnant or breastfeeding women
- Serum alanine aminotransferase or aspartate aminotransferase levels or total bilirubin >3.0×ULN
- Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
- Prior exposure to sotatercept or known allergic reaction to sotatercept, its excipients or luspatercept
- History of pneumonectomy
- Untreated more than mild obstructive sleep apnea
- History of known pericardial constriction
- History of restrictive or congestive cardiomyopathy
- Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) >500 ms during the screening period
- Personal or family history of long QT syndrome or sudden cardiac death
- Left ventricular ejection fraction <45% on historical echocardiogram within 1 year prior to the screening visit
- Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the screening visit
- Cerebrovascular accident within 3 months prior to the screening visit
- Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
- Currently on dialysis or anticipated need for dialysis within the next 12 months
Sites / Locations
- Arizona Pulmonary Specialists ( Site 1010)Recruiting
- David Geffen School of Medicine at UCLA ( Site 1068)Recruiting
- University of California Irvine ( Site 1086)Recruiting
- University of California San Diego Medical Center ( Site 1002)Recruiting
- University of California San Francisco ( Site 1019)Recruiting
- University of Colorado Hospital ( Site 1013)Recruiting
- The George Washington University Medical Faculty Associates ( Site 1025)Recruiting
- Mayo Clinic Jacksonville - PPDS ( Site 1045)Recruiting
- AdventHealth Medical Group Advanced Lung Disease ( Site 1058)Recruiting
- Northside Hospital ( Site 1073)Recruiting
- University Of Iowa Hospitals and Clinics ( Site 1050)Recruiting
- University of Kansas Medical Center ( Site 1020)Recruiting
- Tufts Medical Center - PPDS ( Site 1012)Recruiting
- Brigham and Women's Hospital ( Site 1014)Recruiting
- University of Michigan ( Site 1011)Recruiting
- Washington University School of Medicine ( Site 1022)Recruiting
- University of New Mexico Health Sciences Center ( Site 1048)Recruiting
- University of Rochester Medical Center - PPDS ( Site 1039)Recruiting
- Duke University Medical Center ( Site 1026)Recruiting
- University of Cincinnati Medical Center ( Site 1035)Recruiting
- The Cleveland Clinic Foundation. ( Site 1065)Recruiting
- Medical University of South Carolina - PPDS ( Site 1003)Recruiting
- Statcare Pulmonary Consultants - Knoxville ( Site 1031)Recruiting
- Medical College of Wisconsin - Froedtert Hospital ( Site 1051)Recruiting
- St Vincent's Hospital Sydney ( Site 1102)Recruiting
- John Hunter Hospital ( Site 1101)Recruiting
- Hôpital Erasme ( Site 1402)Recruiting
- UZ Leuven Campus Gasthuisberg ( Site 1401)Recruiting
- Peter Lougheed Centre ( Site 2102)Recruiting
- Jewish General Hospital ( Site 2103)Recruiting
- Hôpitaux Universitaires de Strasbourg ( Site 1307)Recruiting
- Centre Hospitalier Universitaire de Toulouse. ( Site 1315)Recruiting
- CHU de Nancy - Hôpital de Brabois Adultes ( Site 1308)Recruiting
- CHRU Lille ( Site 1306)Recruiting
- Hôpital Louis Pradel ( Site 1317)Recruiting
- CHU Bicêtre ( Site 1304)Recruiting
- CHU de Poitiers ( Site 1316)Recruiting
- Thoraxklinik-Heidelberg gGmbH ( Site 1509)Recruiting
- Krankenhaus Neuwittelsbach ( Site 1510)Recruiting
- Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)Recruiting
- Medizinische Hochschule Hannover ( Site 1505)
- Uniklinik Köln ( Site 1511)Recruiting
- Universitätsklinikum des Saarlandes ( Site 1513)Recruiting
- Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)Recruiting
- Lady Davis Carmel Medical Center ( Site 1705)Recruiting
- Ospedale S. Giuseppe Multimedica ( Site 2403)Recruiting
- La Sapienza-Università di Roma-Policlinico Umberto I ( Site 2402)Recruiting
- Instituto Nacional De Cardiologia Dr. Ignacio Chavez ( Site 2503)Recruiting
- Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 2504)Recruiting
- Unidad de Investigación Clínica en Medicina, S.C ( Site 2505)Recruiting
- VU Medisch Centrum ( Site 2601)Recruiting
- Hospital Universitario 12 de Octubre ( Site 1603)Recruiting
- Royal Papworth Hospital ( Site 1208)Recruiting
- Royal Brompton Hospital ( Site 1206)Recruiting
- Imperial College Healthcare NHS Trust ( Site 1203)Recruiting
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Placebo plus background PAH therapy
Sotatercept plus background PAH therapy
Placebo administered subcutaneously (SC) every 21 days plus background PAH therapy
Sotatercept at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, SC every 21 days plus background PAH therapy