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

NCT04945460 | Completed Phase 2 DMC FDA Drug

• 6 other identifiers: 7962-007A011-16MK-7962-0072023-509141-12-00U1111-1309-64332021-003020-32
• Study Type: interventional
• Target: 164
• Locations: 12 countries
• Sites: 119

Brief 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).

Conditions

Hypertension, Pulmonary

Keywords

Pulmonary, hypertension, Cpc PH, HFpEF, sotatercept

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 24

  Baseline and Week 24

• Time to First Clinical Worsening Event (TTCW) at Weeks 24

  Week 24

• Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24

  Baseline and Week 24

• Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 24

  Baseline and Week 24

• Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 24

  Baseline and Week 24

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks in the placebo-controlled treatment period.

Drug: Placebo

Sotatercept 0.3 mg/kg

EXPERIMENTAL

Participants will receive sotatercept SC at a dose level of 0.3 mg/kg Q3W for 24 weeks in the placebo-controlled treatment period.

Drug: Sotatercept 0.3 mg/kg

Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg

EXPERIMENTAL

Sotatercept SC at a starting dose level of 0.3 mg/kg for 3 dosing visits (Q3W), then escalating to 0.7 mg/kg SC on the fourth dosing visit and Q3W for the remainder of the 24-week treatment Period.

Drug: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg

Interventions

Sotatercept 0.3 mg/kg DRUG

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.

Also known as: ACE-011

Sotatercept 0.3 mg/kg

Placebo DRUG

Administered by subcutaneous injection

Placebo

Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg DRUG

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.

Also known as: ACE-011

Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria to be enrolled in this proof-of-concept study:
• Age 18 to 85 years
• 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
• 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
• New York Heart Association FC of II or III
• Six-minute Walk Distance ≥100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value
• 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
• 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

You may not qualify if:

• Participants will be excluded from the study if any of the following criteria are met:
• A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
• 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)
• 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

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (119)

PULMONARY ASSOCIATES, P.A. ( Site 1008)

Phoenix, Arizona, 85032, United States

Location

University of Arizona ( Site 1006)

Tucson, Arizona, 85724-0001, United States

Location

Scripps Clinic ( Site 4001)

La Jolla, California, 92037-1205, United States

Location

Cedars Sinai Medical Center ( Site 1082)

Los Angeles, California, 90048, United States

Location

University of California Irvine ( Site 1086)

Orange, California, 92868, United States

Location

Jeffrey S.Sager MD Medical Corporation ( Site 1060)

Santa Barbara, California, 93105-5311, United States

Location

Stanford University ( Site 1024)

Stanford, California, 94305, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)

Torrance, California, 90502, United States

Location

University Of Colorado ( Site 1013)

Aurora, Colorado, 80045, United States

Location

South Denver Cardiology Associates ( Site 1091)

Littleton, Colorado, 80120, United States

Location

Winchester Chest Clinic ( Site 1093)

New Haven, Connecticut, 06519-1304, United States

Location

The George Washington University Medical Faculty Associates ( Site 1025)

Washington D.C., District of Columbia, 20037-3201, United States

Location

Bay Area Cardiology ( Site 1071)

Brandon, Florida, 33511, United States

Location

Mayo Clinic Jacksonville - PPDS ( Site 1045)

Jacksonville, Florida, 32224, United States

Location

AdventHealth Orlando ( Site 1058)

Orlando, Florida, 32803, United States

Location

Tampa General Hospital ( Site 1043)

Tampa, Florida, 33606, United States

Location

Piedmont Atlanta Hospital ( Site 1085)

Atlanta, Georgia, 30309-1281, United States

Location

Emory University ( Site 1030)

Atlanta, Georgia, 30322-1013, United States

Location

Saint Alphonsus Regional Medical Center ( Site 1097)

Boise, Idaho, 83704-8880, United States

Location

University of Illinois Hospital ( Site 1095)

Chicago, Illinois, 60612, United States

Location

IU Health Advanced Heart and Lung Care ( Site 1092)

Indianapolis, Indiana, 46202-1218, United States

Location

Ascension Medical Group St. Vincent ( Site 1076)

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Hospital and Clinics ( Site 1050)

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center ( Site 1020)

Kansas City, Kansas, 66160, United States

Location

Norton Pulmonary Specialists ( Site 1066)

Louisville, Kentucky, 40202, United States

Location

University of Louisville ( Site 1099)

Louisville, Kentucky, 40202, United States

Location

University Medical Center New Orleans ( Site 1057)

New Orleans, Louisiana, 70112, United States

Location

Tufts Medical Center - PPDS ( Site 1012)

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital [Boston, MA] ( Site 1014)

Boston, Massachusetts, 02115, United States

Location

University of Michigan ( Site 1011)

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Hospitals ( Site 1062)

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine [Saint Louis, MO] ( Site 1022)

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center ( Site 1053)

Omaha, Nebraska, 68198, United States

Location

Pulmonary Health Physicians ( Site 1080)

Liverpool, New York, 13088, United States

Location

Weill Cornell Medical College ( Site 1046)

New York, New York, 10021-9800, United States

Location

University of Rochester Medical Center - PPDS ( Site 1039)

Rochester, New York, 14642, United States

Location

Duke University Medical Center ( Site 1026)

Durham, North Carolina, 27710-4000, United States

Location

The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center ( Site 1005)

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation ( Site 1065)

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center ( Site 1032)

Columbus, Ohio, 43210, United States

Location

University of Toledo Medical Center ( Site 1070)

Toledo, Ohio, 43614, United States

Location

Oregon Health Science University ( Site 1054)

Portland, Oregon, 97126, United States

Location

Allegheny General Hospital ( Site 1088)

Pittsburgh, Pennsylvania, 15212-4737, United States

Location

Lankenau Institute for Medical Research ( Site 1089)

Wynnewood, Pennsylvania, 19096, United States

Location

Rhode Island Hospital ( Site 1033)

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina - PPDS ( Site 1003)

Charleston, South Carolina, 29425-0001, United States

Location

Statcare Pulmonary Consultants - Knoxville ( Site 1031)

Knoxville, Tennessee, 37919, United States

Location

Baylor University Medical Center ( Site 1096)

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center ( Site 4002)

Dallas, Texas, 75390, United States

Location

Intermountain Medical Center ( Site 1079)

Murray, Utah, 84107, United States

Location

Inova Heart and Vascular Institute ( Site 1078)

Falls Church, Virginia, 22042, United States

Location

Bon Secours St. Mary's Hospital ( Site 1069)

Richmond, Virginia, 23226, United States

Location

West Virginia University ( Site 1081)

Morgantown, West Virginia, 26506, United States

Location

Aurora St Luke's Medical Center ( Site 1083)

Milwaukee, Wisconsin, 53215, United States

Location

Froedtert Hospital & the Medical College of Wisconsin ( Site 1051)

Milwaukee, Wisconsin, 53226, United States

Location

Hôpital Erasme ( Site 1402)

Anderlecht, Bruxelles-Capitale, Region de, 1070, Belgium

Location

UZ Leuven - Campus Gasthuisberg ( Site 1401)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

University Of Alberta ( Site 2101)

Edmonton, Alberta, T6G 2B7, Canada

Location

Hamilton General Hospital-Special Immunology Services Clinic ( Site 2110)

Hamilton, Ontario, L8L 2X2, Canada

Location

University Health Network ( Site 2109)

Toronto, Ontario, M5G 2N2, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie ( Site 2107)

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Hôpital Pasteur - CHU Nice ( Site 1311)

Nice, Alpes-Maritimes, 06000, France

Location

Centre Hospitalier Universitaire du Besancon ( Site 1324)

Besançon, Doubs, 25000, France

Location

Hopital de Rangueil du Toulouse ( Site 1322)

Toulouse, Haute-Garonne, 31400, France

Location

CHU Montpellier Hôpital Arnaud de VIlleneuve ( Site 1301)

Montpellier, Herault, 34090, France

Location

Hôpital Pontchaillou ( Site 1319)

Rennes, Ille-et-Vilaine, 35033, France

Location

Centre Hospitalier Universitaire de Grenoble ( Site 1303)

Grenoble, Isere, 38043, France

Location

CHU de Nantes - Hoptal Nord Laennec ( Site 1309)

Nantes, Loire-Atlantique, 44000, France

Location

CHU Angers ( Site 1313)

Angers, Maine-et-Loire, 49933, France

Location

CHRU de Nancy Hopitaux de Brabois ( Site 1308)

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54500, France

Location

CHRU Lille ( Site 1306)

Lille, Nord, 59037, France

Location

CHU de Rouen ( Site 1323)

Rouen, Seine-Maritime, 76000, France

Location

Centre Hospitalier Universitaire de Bicetre ( Site 1304)

Le Kremlin-Bicêtre, Val-de-Marne, 94270, France

Location

Thoraxklinik-Heidelberg gGmbH ( Site 1509)

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Krankenhaus Neuwittelsbach ( Site 1510)

München, Bavaria, 80639, Germany

Location

University Hospital Regensburg ( Site 1503)

Regensburg, Bavaria, 93053, Germany

Location

Kerckhoff-Klinik-Forschungs-GmbH ( Site 1514)

Bad Nauheim, Hesse, 61231, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH ( Site 1512)

Giessen, Hesse, 35392, Germany

Location

Medizinische Hochschule Hannover ( Site 1505)

Hanover, Lower Saxony, 30625, Germany

Location

Uniklinik Köln ( Site 1511)

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Universitaetsmedizin Johannes Gutenberg Universitaet Mainz ( Site 1515)

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)

Dresden, Saxony, 01307, Germany

Location

DRK Kliniken Berlin Westend ( Site 1507)

Berlin, 14050, Germany

Location

Assuta Ashdod Medical Center ( Site 1710)

Ashdod, 7747629, Israel

Location

Shamir Medical Center Assaf Harofeh ( Site 1713)

Be’er Ya‘aqov, 70300, Israel

Location

Rambam Health Corp. ( Site 1716)

Haifa, 3109601, Israel

Location

Lady Davis Carmel Medical Center ( Site 1705)

Haifa, 3436212, Israel

Location

Edith Wolfson Medical Center ( Site 1717)

Holon, 5810001, Israel

Location

Shaare Zedek Medical Center ( Site 1715)

Jerusalem, 91031, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 1711)

Jerusalem, 91120, Israel

Location

Meir Medical Center. ( Site 1707)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 1703)

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center ( Site 1712)

Rehovot, 7610001, Israel

Location

ZIV Medical Center ( Site 1704)

Safed, 13100, Israel

Location

Tel Aviv Sourasky Medical Center ( Site 1714)

Tel Aviv, 64239, Israel

Location

AOU di Bologna Policlinico S Orsola Malpighi ( Site 2409)

Bologna, Emilia-Romagna, 40138, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)

Trieste, Friuli Venezia Giulia, 34149, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo ( Site 2406)

Monza, Lombardy, 20900, Italy

Location

Fondazione IRCCS-Policlinico San Matteo ( Site 2401)

Pavia, Lombardy, 27100, Italy

Location

Ospedale SS Annunziata ( Site 2408)

Sassari, Sardinia, 07100, Italy

Location

ASST Papa Giovanni XXIII ( Site 2410)

Bergamo, 24127, Italy

Location

Azienda Policlinico Umberto I ( Site 2402)

Roma, 00161, Italy

Location

Unidad de Investigacion Clinica En Medicina SC ( Site 2505)

Monterrey, Nuevo León, 64710, Mexico

Location

Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2801)

Krakow, Lesser Poland Voivodeship, 31-202, Poland

Location

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 2806)

Lubin, Lublin Voivodeship, 20-718, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)

Otwock, Masovian Voivodeship, 05-400, Poland

Location

Państwowy Instytut Medyczny MSWiA ( Site 2805)

Warsaw, Masovian Voivodeship, 02-507, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku - Marii Sklodowskiej-Curie 24A ( Site 2803)

Bialystok, Podlaskie Voivodeship, 15-276, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie ( Site 2804)

Szczecin, West Pomeranian Voivodeship, 70-111, Poland

Location

Wojewodzki Specjalistyczny Szpital im dr WI Bieganskiego w Lodzi ( Site 2807)

Lodz, Łódź Voivodeship, 91-347, Poland

Location

Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)

Majadahonda, Madrid, 28222, Spain

Location

Hospital Costa del Sol ( Site 1613)

Marbella, Malaga, 29603, Spain

Location

Hospital Clinic de Barcelona ( Site 1602)

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre ( Site 1603)

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Macarena ( Site 1612)

Seville, 41009, Spain

Location

Hospital Universitario de Toledo ( Site 1607)

Toledo, 41007, Spain

Location

Sahlgrenska Universitetssjukhuset ( Site 3201)

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Imperial College Healthcare NHS Trust ( Site 1203)

London, London, City of, W12 0HS, United Kingdom

Location

Related Publications (1)

• Gomberg-Maitland M, Tedford RJ, Langleben D, Rosenkranz S, Miller B, Jones AD, Urbinati A, McMullan CJ, Cornell AG, Vachiery JL. Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure: Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study. Circulation. 2026 Mar 29. doi: 10.1161/CIRCULATIONAHA.126.079918. Online ahead of print.

  PMID: 41904795 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hypertension, Pulmonary; Hypertension

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each eligible participant will be randomly assigned in a 1:1:1 ratio to 1 of the 3 treatment groups during the Treatment Period: Arm 1: Treatment Group 1: Placebo delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks Arm 2: Treatment Group 2: Sotatercept SC at a dose level of 0.3 mg/kg Q3W for 24 weeks Arm 3: Treatment Group 3: Sotatercept SC at a starting dose level of 0.3 mg/kg for 3 dosing visits (Q3W), then escalating to 0.7 mg/kg SC on the fourth dosing visit and Q3W for the remainder of the 24-week Treatment Period

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 30, 2021
• Study Start: December 29, 2021
• Primary Completion: September 5, 2025
• Study Completion: April 9, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (7); US (56); ES (6); IL (12); BE (2); CA (4); FR (12); ME (1); DE (10); PL (7); SE (1); GB (1)