A Study of Sotatercept for the Treatment of Cpc-PH Due to HFpEF (MK-7962-007/A011-16)

Hypertension, Pulmonary Clinical Trial

— CADENCE  

Official title:

A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of Sotatercept Versus Placebo for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) Due to Heart Failure With Preserved Ejection Fraction (HFpEF)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04945460
• Other study ID #: 7962-007
• Secondary ID: A011-16MK-7962-0
• Status: Recruiting
• Phase: Phase 2
• Start date: December 29, 2021
• Est. completion date: February 20, 2027

Study information

• Verified date: June 2024
• Source: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of sotatercept versus placebo in adults with Cpc-PH due to HFpEF.

The objective of this study is to evaluate the efficacy, safety and tolerability of sotatercept versus placebo in adults with Cpc-PH due to HFpEF. Efficacy is measured by change from baseline in pulmonary vascular resistance (PVR, primary endpoint) and 6-minute walk distance (6MWD, key secondary endpoint).

Description:

Participants enrolled in the study will have a diagnosis of Cpc-PH due to HFpEF with New York Heart Association (NYHA) functional class (FC) II or III. Participants will be randomly assigned in a 1:1:1 ratio to 1 of the 3 treatment groups (placebo, 0.3mg/kg sotatercept and 0.7mg/kg sotatercept) during the placebo-controlled Treatment Period. In the extension phase, sotatercept-treated participants will continue on their current dose. Placebo participants will be re-randomized in a 1:1 ratio to one of the two sotatercept treatment groups utilized in the placebo-controlled Treatment Period. Each participant will be enrolled in the study for up to 114 weeks, including a 28-day Screening Period, a 24-week, double-blind, placebo-controlled Treatment Period, an 18-month Extension Period, and an 8-week Follow-up Period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 20, 2027
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

Participants must meet the following criteria to be enrolled in this proof-of-concept study:

1. Age 18 to 85 years

2. Clinical diagnosis of HFpEF:

• Left ventricular ejection fraction =50%, with no history of LVEF below 45% in more than two consecutive measurements under stable conditions

3. Demonstrated Cpc-PH by all of the following:

• Baseline RHC performed within 28 days of randomization documenting a minimum PVR of =320 dyn•sec/cm5 (4 wood units)

• Mean pulmonary arterial pressure (mPAP) of >20 mmHg

• Pulmonary capillary wedge pressure (PCWP) >15 mmHg but < 30 mmHg

4. New York Heart Association FC of II or III

5. Six-minute Walk Distance =100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value

6. Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for =30 days prior to Visit 1. Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within 30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1. Anticoagulation may be suspended for RHC if necessary.

7. Women of childbearing potential must:

• Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; must agree to ongoing 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: use highly effective contraception without interruption for at least 28 days prior to starting the investigational product AND agree 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 drug

8. Male participants must:

• Agree to use a condom, defined as a male latex condom or non latex 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 drug

9. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements

10. Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study

11. Ability to understand and provide documented consent for participation

Exclusion Criteria:

Participants will be excluded from the study if any of the following criteria are met:

1. A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5

2. Clinically significant and active lung disease:

• Chronic obstructive pulmonary disease with post-bronchodilator forced expiratory volume in the first second (FEV1) <60% predicted

• Restrictive lung disease with total lung capacity <70% predicted

• More than mild interstitial lung disease (ILD), with FVC<70% or FEV1<60% predicted (still appropriate if absence of more than mild ILD, fibrosis, or COPD on computed tomography [CT] imaging)

3. Cardiovascular co-morbidities, which include any of the following:

• History of more than mild mitral or aortic stenosis

• Ongoing more than mild mitral or aortic regurgitation

• More than one valve replacement or repair (mechanical or biomechanical) or anticipation of any valve replacement or repair

• Severe tricuspid regurgitation due to primary valvular disease

• Occurrence of myocardial infarction, acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1

• History of serious life-threatening or hemodynamically significant arrhythmia

• History of or anticipated heart transplant or ventricular assist device implantation

• History of implantable cardioverter defibrillator placement or anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening

• Anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening or history of implantable cardioverter defibrillator placement

• Occurrence of myocardial infarction within 180 days of Visit 1

• History of known pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy

• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mmHg or sitting diastolic blood pressure >110 mmHg during Screening after a period of rest

• Systemic hypotension as evidenced by sitting systolic blood pressure <90 mmHg or sitting diastolic blood pressure <50 mmHg during Screening

• Resting heart rate of <45 bpm or >115 bpm

• Stroke within 90 days of Visit 1

• Acutely decompensated HF that required hospitalization within 30 days of Visit 1

• Electrocardiogram during Screening Period with Fridericia's corrected QT interval (QTcF) >470 msec for males or >480 msec for females, or >500 msec if a ventricular conduction defect (right bundle branch block; left bundle branch block; or interventricular conduction delay) is present

• Personal or family history of Brugada syndrome, sudden cardiac arrest or unexplained sudden cardiac death or arrest

• Personal or family history of long QT syndrome unless the participant's ECG shows a normal QTc

• Arrhythmogenic right ventricular dysplasia (ARVD) unless the participant has a recent cardiac MRI that shows no evidence of this diagnosis

4. Hospitalization for any worsening of medical conditions or any significant surgery per investigator within 30 days of Visit 1.

5. Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators) within 30 days of Visit 1.The use of an oral phosphodiesterase type 5 inhibitor, if only indicated for erectile dysfunction, is permitted, if not administered within 48 hours of a study visit or procedure.

6. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin,or levosimendan) within 30 days of Visit 1

7. Received erythropoietin within 6 months of Visit 1.

8. Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), with severe hepatic impairment and/or cirrhosis (e.g., hepatic encephalopathy)

9. Prior exposure to sotatercept or luspatercept.

10. 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 consent.

11. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days of Visit 1 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).

12. Any of the following clinical laboratory values prior to Visit 1 as specified:

• Hemoglobin (Hgb) above the gender-specific upper limit of normal (ULN) per local laboratory test within 28 days of Visit 1or <10 g/dL per local laboratory within 28 days of Visit 1

• Serum alanine aminotransferase or aspartate aminotransferase levels >3× ULN or total bilirubin >3× ULN within 28 days of Visit 1

• Estimated glomerular filtration rate <30 ml/min/1.73 m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of Visit 1 or required renal replacement therapy within 90 days of Visit 1

• Glycated hemoglobin (HbA1c) >10% within 28 days of Visit 1

• Platelet count < 75,000/mm3 within 28 days of Visit 1

13. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product .

14. Major surgery within 60 days of Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1.

15. Prior organ transplantation (e.g., heart, lung, liver, kidney), bone marrow transplantation, or life expectancy of < 12 months.

16. Pregnancy or breastfeeding in females.

17. Active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or = 2 squamous cell carcinomas of the skin.

18. History of clinically significant (as determined by the investigator) endocrine, hematologic, hepatic, (auto)immune, infectious (requiring chronic antibiotics), metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study.

19. Body mass index =50 kg/m2.

20. More than mild obstructive sleep apnea (treated or untreated).

21. Any non-cardiopulmonary condition or acute/chronic impairment(s) (other than dyspnea) that limits the ability to perform 6-minute walk test (6MWT).

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• Sotatercept 0.3 mg/kg
Administered by subcutaneous injection. Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1.
• Placebo
Administered by subcutaneous injection
• Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg
Administered by subcutaneous injection. Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1.

Locations

Country	Name	City	State
Belgium	Hôpital Erasme ( Site 1402)	Anderlecht	Bruxelles-Capitale, Region De
Belgium	UZ Leuven - Campus Gasthuisberg ( Site 1401)	Leuven	Vlaams-Brabant
Canada	University Of Alberta ( Site 2101)	Edmonton	Alberta
Canada	Hamilton General Hospital-Special Immunology Services Clinic ( Site 2110)	Hamilton	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie ( Site 2107)	Sainte Foy	Quebec
Canada	University Health Network ( Site 2109)	Toronto	Ontario
France	CHU Angers ( Site 1313)	Angers	Maine-et-Loire
France	Centre Hospitalier Universitaire du Besancon ( Site 1324)	Besançon	Doubs
France	Centre Hospitalier Universitaire de Grenoble ( Site 1303)	Grenoble cedex 09	Isere
France	Centre Hospitalier Universitaire de Bicetre ( Site 1304)	Le Kremlin Bicêtre	Val-de-Marne
France	CHRU Lille ( Site 1306)	Lille	Nord
France	CHU Montpellier Hôpital Arnaud de VIlleneuve ( Site 1301)	Montpellier	Herault
France	CHU de Nantes - Hoptal Nord Laennec ( Site 1309)	Nantes	Loire-Atlantique
France	Hôpital Pasteur - CHU Nice ( Site 1311)	Nice	Alpes-Maritimes
France	Hôpital Pontchaillou ( Site 1319)	Rennes	Ille-et-Vilaine
France	CHU de Rouen ( Site 1323)	Rouen	Seine-Maritime
France	Hopital de Rangueil du Toulouse ( Site 1322)	Toulouse	Haute-Garonne
France	CHRU de Nancy Hopitaux de Brabois ( Site 1308)	Vandœuvre-lès-Nancy	Meurthe-et-Moselle
Germany	Kerckhoff-Klinik-Forschungs-GmbH ( Site 1514)	Bad Nauheim	Hessen
Germany	DRK Kliniken Berlin Westend ( Site 1507)	Berlin
Germany	Uniklinik Köln ( Site 1511)	Cologne	Nordrhein-Westfalen
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)	Dresden	Sachsen
Germany	Universitätsklinikum Gießen und Marburg GmbH ( Site 1512)	Gießen	Hessen
Germany	Medizinische Hochschule Hannover ( Site 1505)	Hannover	Niedersachsen
Germany	Thoraxklinik-Heidelberg gGmbH ( Site 1509)	Heidelberg	Baden-Wurttemberg
Germany	Universitaetsmedizin Johannes Gutenberg Universitaet Mainz ( Site 1515)	Mainz	Rheinland-Pfalz
Germany	Krankenhaus Neuwittelsbach ( Site 1510)	München	Bayern
Germany	University Hospital Regensburg ( Site 1503)	Regensburg	Bayern
Israel	Assuta Ashdod Medical Center ( Site 1710)	Ashdod
Israel	Shamir Medical Center Assaf Harofeh ( Site 1713)	Be'er Ya'akov
Israel	Lady Davis Carmel Medical Center ( Site 1705)	Haifa
Israel	Rambam Health Corp. ( Site 1716)	Haifa
Israel	Edith Wolfson Medical Center ( Site 1717)	Holon
Israel	Hadassah Ein Kerem Medical Center ( Site 1711)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 1715)	Jerusalem
Israel	Meir Medical Center ( Site 1707)	Kfar Saba
Israel	Rabin Medical Center ( Site 1703)	Petah Tiqwa
Israel	Kaplan Medical Center ( Site 1712)	Rehovot
Israel	ZIV Medical Center ( Site 1704)	Safed
Israel	Tel Aviv Sourasky Medical Center ( Site 1714)	Tel Aviv
Italy	ASST Papa Giovanni XXIII ( Site 2410)	Bergamo
Italy	AOU di Bologna Policlinico S Orsola Malpighi ( Site 2409)	Bologna	Emilia-Romagna
Italy	Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo ( Site 2406)	Monza	Lombardia
Italy	Fondazione IRCCS-Policlinico San Matteo ( Site 2401)	Pavia	Lombardia
Italy	Azienda Policlinico Umberto I ( Site 2402)	Roma
Italy	Ospedale SS Annunziata ( Site 2408)	Sassari	Sardegna
Italy	Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)	Trieste	Friuli-Venezia Giulia
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku - Marii Sklodowskiej-Curie 24A ( Site 2803)	Bialystok	Podlaskie
Poland	Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2801)	Krakow	Malopolskie
Poland	Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 2806)	Lubin	Lubelskie
Poland	Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)	Otwock	Mazowieckie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie ( Site 2804)	Szczecin	Zachodniopomorskie
Poland	Panstwowy Instytut Medyczny MSWiA ( Site 2805)	Warszawa	Mazowieckie
Spain	Hospital Clinic de Barcelona ( Site 1602)	Barcelona
Spain	Hospital Universitario 12 de Octubre ( Site 1603)	Madrid
Spain	Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)	Majadahonda	Madrid
Spain	Hospital Costa del Sol ( Site 1613)	Marbella	Malaga
Spain	Hospital Universitario Virgen Macarena ( Site 1612)	Sevilla
Spain	Hospital Universitario de Toledo ( Site 1607)	Toledo
Sweden	Sahlgrenska Universitetssjukhuset ( Site 3201)	Goteburg	Vastra Gotalands Lan
United Kingdom	Imperial College Healthcare NHS Trust ( Site 1203)	London	London, City Of
United States	University of Michigan ( Site 1011)	Ann Arbor	Michigan
United States	Emory University ( Site 1030)	Atlanta	Georgia
United States	Piedmont Atlanta Hospital ( Site 1085)	Atlanta	Georgia
United States	University Of Colorado ( Site 1013)	Aurora	Colorado
United States	Saint Alphonsus Regional Medical Center ( Site 1097)	Boise	Idaho
United States	Brigham and Women's Hospital [Boston, MA] ( Site 1014)	Boston	Massachusetts
United States	Tufts Medical Center - PPDS ( Site 1012)	Boston	Massachusetts
United States	Bay Area Cardiology ( Site 1071)	Brandon	Florida
United States	Medical University of South Carolina - PPDS ( Site 1003)	Charleston	South Carolina
United States	University of Illinois Hospital ( Site 1095)	Chicago	Illinois
United States	The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)	Cincinnati	Ohio
United States	Cleveland Clinic Foundation ( Site 1065)	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center ( Site 1005)	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center ( Site 1032)	Columbus	Ohio
United States	Duke University Medical Center ( Site 1026)	Durham	North Carolina
United States	Rhode Island Hospital ( Site 1033)	East Providence	Rhode Island
United States	Inova Heart and Vascular Institute ( Site 1078)	Falls Church	Virginia
United States	Ascension Medical Group St. Vincent ( Site 1076)	Indianapolis	Indiana
United States	IU Health Advanced Heart and Lung Care ( Site 1092)	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics ( Site 1050)	Iowa City	Iowa
United States	Mayo Clinic Jacksonville - PPDS ( Site 1045)	Jacksonville	Florida
United States	University of Kansas Medical Center ( Site 1020)	Kansas City	Kansas
United States	Statcare Pulmonary Consultants - Knoxville ( Site 1031)	Knoxville	Tennessee
United States	South Denver Cardiology Associates ( Site 1091)	Littleton	Colorado
United States	Pulmonary Health Physicians ( Site 1080)	Liverpool	New York
United States	Cedars Sinai Medical Center ( Site 1082)	Los Angeles	California
United States	Norton Pulmonary Specialists ( Site 1066)	Louisville	Kentucky
United States	Aurora St Luke's Medical Center ( Site 1083)	Milwaukee	Wisconsin
United States	Froedtert Hospital & the Medical College of Wisconsin ( Site 1051)	Milwaukee	Wisconsin
United States	University of Minnesota Hospitals ( Site 1062)	Minneapolis	Minnesota
United States	West Virginia University ( Site 1081)	Morgantown	West Virginia
United States	Intermountain Medical Center ( Site 1079)	Murray	Utah
United States	Winchester Chest Clinic ( Site 1093)	New Haven	Connecticut
United States	University Medical Center New Orleans ( Site 1057)	New Orleans	Louisiana
United States	Weill Cornell Medical College ( Site 1046)	New York	New York
United States	University of Nebraska Medical Center ( Site 1053)	Omaha	Nebraska
United States	University of California Irvine ( Site 1086)	Orange	California
United States	AdventHealth Orlando ( Site 1058)	Orlando	Florida
United States	PULMONARY ASSOCIATES, P.A. ( Site 1008)	Phoenix	Arizona
United States	Allegheny General Hospital ( Site 1088)	Pittsburgh	Pennsylvania
United States	Oregon Health Science University ( Site 1054)	Portland	Oregon
United States	Bon Secours St. Mary's Hospital ( Site 1069)	Richmond	Virginia
United States	University of Rochester Medical Center - PPDS ( Site 1039)	Rochester	New York
United States	Washington University School of Medicine [Saint Louis, MO] ( Site 1022)	Saint Louis	Missouri
United States	Jeffrey S.Sager MD Medical Corporation ( Site 1060)	Santa Barbara	California
United States	Stanford University ( Site 1024)	Stanford	California
United States	Tampa General Hospital ( Site 1043)	Tampa	Florida
United States	University of Toledo Medical Center ( Site 1070)	Toledo	Ohio
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)	Torrance	California
United States	University of Arizona ( Site 1006)	Tucson	Arizona
United States	The George Washington University Medical Faculty Associates ( Site 1025)	Washington	District of Columbia
United States	Lankenau Institute for Medical Research ( Site 1089)	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization (RHC).	Baseline and Week 24
Secondary	Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 24	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity.	Baseline and Week 24
Secondary	Time to First Clinical Worsening Event (TTCW) at Weeks 24	Clinical Worsening events are defined as the number of weeks from first dose date to any of the following: Hospitalization due to a cardiopulmonary indication (a non-elective hospitalization lasting at least 24 hours in duration caused by clinical conditions directly related to Pulmonary Hypertension and/or Heart Failure); Administration of intravenous diuretics or subcutaneous (SC) furosemide; Death (all causes); Decrease in 6 minute walk distance (6MWD) by = 15% from baseline confirmed by 2 tests at least 4 hours, but no more than 1 week apart.	Week 24
Secondary	Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24	mPAP is calculated from systolic and diastolic pulmonary artery pressure measured by right heart catheterization.	Baseline and Week 24
Secondary	Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 24	PCWP is an indirect estimate of left atrial pressure measured in right heart catheterization.	Baseline and Week 24
Secondary	Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 24	TAPSE is an echocardiographic measurement of tricuspid valve annulus movement, as an indicator of right heart function.	Baseline and Week 24
Secondary	Change From Baseline in Right Ventricular Fractional Area Change (RVFAC) at Week 24	RVFAC is an echocardiographic measurement of percent change between right ventricular area during diastole and systole, as an indicator of right heart function.	Baseline and Week 24
Secondary	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24	LVEF is an echocardiographic measurement of percent change between left ventricular volume during diastole and systole, as an indicator of left heart function.	Baseline and Week 24
Secondary	Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 24	IVRT is an echocardiographic measurement of the interval between closure of the aortic valve, to onset of filling by opening of the mitral valve. It is used as an indicator of diastolic dysfunction.	Baseline and Week 24
Secondary	Change From Baseline in ratio of mitral inflow velocity I to mitral annular velocity'(e') (E/e' ratio) at Week 24	E/e' is a ratio measured in echocardiography as an indicator of diastolic function.	Baseline and Week 24
Secondary	Change From Baseline in the Ratio of the Peak Velocity Flow of the E Wave in Early Diastole to Peak Velocity Flow of the A Wave in Late Diastole (E/A Ratio) at Week 24	E/A is a ratio measured in echocardiography as an indicator of diastolic function.	Baseline and Week 24
Secondary	Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) at Week 24	NT-proBNP is a circulating biomarker that reflects myocardial stretch.	Baseline and Week 24
Secondary	Change From Baseline in New York Heart Association Functional Class (NYHA FC) at Week 24	NYHA FC classifies the extent of heart failure.	Baseline and Week 24
Secondary	Change From Baseline in Myocardial Contraction Fraction (MCF) at Week 24	MCF is an echocardiographic measurement that determines the ratio of left ventricular stroke volume to myocardial volume and is an indicator of left ventricular systolic function.	Baseline and Week 24
Secondary	Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 48	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity.	Baseline and Week 48
Secondary	Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 48	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization.	Baseline and Week 48
Secondary	Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 48	mPAP is calculated from systolic and diastolic pulmonary artery pressure measured by right heart catheterization.	Baseline and Week 48
Secondary	Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 48	PCWP is an indirect estimate of left atrial pressure measured in right heart catheterization.	Baseline and Week 48
Secondary	Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 48	TAPSE is an echocardiographic measurement of tricuspid valve annulus movement, as an indicator of right heart function.	Baseline and Week 48
Secondary	Change From Baseline in Right Ventricular Fractional Area Change (RVFAC) at Week 48	RVFAC is an echocardiographic measurement of percent change between right ventricular area during diastole and systole, as an indicator of right heart function.	Baseline and Week 48
Secondary	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 48	LVEF is an echocardiographic measurement of percent change between left ventricular volume during diastole and systole, as an indicator of left heart function.	Baseline and Week 48
Secondary	Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 48	IVRT is an echocardiographic measurement of the interval between closure of the aortic valve, to onset of filling by opening of the mitral valve. It is used as an indicator of diastolic dysfunction.	Baseline and Week 48
Secondary	Change From Baseline in E/e' (Early Mitral Inflow Velocity E and Mitral Annular Early Diastolic Velocity e') Ratio at Week 48	E/e' is a ratio measured in echocardiography as an indicator of diastolic function.	Baseline and Week 48
Secondary	Change From Baseline in the Ratio of the Peak Velocity Flow of the E Wave in Early Diastole to Peak Velocity Flow of the A Wave in Late Diastole (E/A Ratio) at Week 48	E/A is a ratio measured in echocardiography as an indicator of diastolic function.	Baseline and Week 48
Secondary	Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) at Week 48	NT-proBNP is a circulating biomarker that reflects myocardial stretch.	Baseline and Week 48
Secondary	Change From Baseline in New York Heart Association Functional Class (NYHA FC) at Week 48	NYHA FC classifies the extent of heart failure.	Baseline and Week 48
Secondary	Change From Baseline in Myocardial Contraction Fraction (MCF) at Week 48	MCF is an echocardiographic measurement that determines the ratio of left ventricular stroke volume to myocardial volume and is an indicator of left ventricular systolic function.	Baseline and Week 48
Secondary	Change From Baseline in Pulmonary Vascular Resistance (PVR) for the Placebo Crossed Over to Sotatercept Cohorts at Week 48 of the Extension Period	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization.	Baseline and Week 48 of the Extension Period
Secondary	Change From Baseline in the 6-minute walk distance (6MWD) for the Placebo Crossed Over to Sotatercept Cohorts at Week 48 of the Extension Period	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity.	Baseline and Week 48 of the Extension Period
Secondary	Change From Baseline in New York Heart Association Functional Class (NYHA FC) for the Placebo Crossed Over to Sotatercept Cohorts at Week 48 of the Extension Period	NYHA FC classifies the extent of heart failure.	Baseline and Week 48 of the Extension Period
Secondary	Change in Pulmonary Vascular Resistance (PVR) for the Placebo Crossed Over to Sotatercept Cohorts From Week 24 to Week 48 of the Extension Period	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization.	From Week 24 to Week 48 of the Extension Period
Secondary	Change in 6-minute Walk Distance (6MWD) for the Placebo Crossed Over to Sotatercept Cohorts From Week 24 to Week 48 of the Extension Period	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity.	From Week 24 to Week 48 of the Extension Period
Secondary	Change in New York Heart Association Functional Class (NYHA FC) for the Placebo Crossed Over to Sotatercept Cohorts From Week 24 to Week 48 of the Extension Period	NYHA FC classifies the extent of heart failure.	From Week 24 to Week 48 of the Extension Period

External Links

•   Merck Clinical Trials Information