Extension Study of Sotatercept in People With Pulmonary Hypertension (MK-7962-023) (HARMONIZE)

A Phase 2, Multicenter, Open-label Extension Study to Evaluate the Effects of Sotatercept for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) With Heart Failure With Preserved Ejection Fraction (HFpEF)

Researchers are looking for new ways to treat people with a type of pulmonary hypertension called combined postcapillary and precapillary pulmonary hypertension (Cpc-PH). This study focuses on Cpc-PH that is caused by heart failure with preserved ejection fraction (HFpEF).

Researchers want to know if the study treatment, sotatercept, can treat people with Cpc-PH caused by HFpEF. This is an extension study, which means people who took part in a certain study on sotatercept for Cpc-PH (called a parent study) may be able to join this study. In this extension study, people will take sotatercept and researchers will follow their health for a longer time.

The main goal of this extension study is to learn about the long-term safety of sotatercept and if people tolerate it over a longer period of time.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Biological: Sotatercept

Detailed Description

This is an extension study for studies MK-7962-007 (NCT04945460) and MK-7962-041 (NCT number pending).

Following protocol amendment 3, all participants in the Sotatercept 0.7 mg/kg arm will switch to the Sotatercept 0.3 mg/kg arm, and new participants will only enroll in the Sotatercept 0.3 mg/kg arm.

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-Capitale, Region de
    • Brussels, Bruxelles-Capitale, Region de, Belgium, 1070
      • Université Libre de Bruxelles - Hôpital Erasme ( Site 0100)
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences Hamilton General Hospital ( Site 0004)
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06000
      • Centre Hospitalier Universitaire de Nice - Hopital Pasteur ( Site 0206)
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Arnaud de Villeneuve ( Site 0200)
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44800
      • Hôpital Nord Guillaume-et-René-Laennec / CHU de Nantes ( Site 0205)
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49100
      • Centre Hopitalier Universitaire d'Angers ( Site 0204)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76031
      • CHU de Rouen ( Site 0203)
  • Val-de-Marne
    • Le Kremlin-Bicêtre, Val-de-Marne, France, 94270
      • Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0202)
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend ( Site 0307)
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH ( Site 0309)
  • Bavaria
    • München, Bavaria, Germany, 80639
      • Krankenhaus Neuwittelsbach ( Site 0310)
  • Hesse
    • Giessen, Hesse, Germany, 35392
      • UKGM Gießen/Marburg ( Site 0312)
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitaetsklinikum Koeln ( Site 0311)
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Johannes Gutenberg Universität Mainz ( Site 0315)
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0301)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus ( Site 0403)
  • Holon, Israel, 5810001
    • Edith Wolfson Medical Center ( Site 0404)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 0402)
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center ( Site 0401)
  • Safed, Israel, 1311001
    • ZIV Medical Center ( Site 0400)
• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo ( Site 0501)
  • Roma, Italy, 00161
    • AOU Policlinico Umberto I ( Site 0500)
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII ( Site 0502)
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Unidad de Investigacion Clinica en Medicina, S.C. ( Site 2505)
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-202
      • Krakowski Szpital Specjalistyczny im. Jana Pawła II-Oddzial Kliniczny Chorob Serca i Naczyn z Podod ( Site 0600)
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-718
      • Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 0601)
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-276
      • Uniwersytecki Szpital Kliniczny w Bialymstoku ( Site 0603)
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial de Barcelona ( Site 0701)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 0702)
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena ( Site 0705)
  • Toledo, Spain, 45007
    • HOSPITAL GENERAL UNIVERSITARIO DE TOLEDO ( Site 0703)
  • Malaga
    • Marbella, Malaga, Spain, 29603
      • Hospital Costa del Sol ( Site 0704)
• Sweden
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, 413 46
      • Sahlgrenska Universitetssjukhuset-Cardiology Research Unit ( Site 0800)
• United Kingdom
  • London, City of
    • London, London, City of, United Kingdom, W12 OHS
      • Hammersmith Hospital-Department of Cardiology ( Site 0900)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates, PA ( Site 1008)
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic John R Anderson V Medical Pavillion ( Site 1004)
    • Santa Barbara, California, United States, 93105
      • Jeffrey S. Sager, MD Medical Corporation ( Site 1060)
    • Stanford, California, United States, 94305
      • Stanford University Medical Center ( Site 1024)
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates ( Site 1091)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale New Haven Hospital ( Site 1093)
  • Florida
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando ( Site 1058)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic ( Site 1030)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists ( Site 1066)
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center ( Site 1053)
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center ( Site 1046)
  • North Carolina
    • Durham, North Carolina, United States, 27710-4000
      • Duke University Medical Center ( Site 1026)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation. ( Site 1065)
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center ( Site 1032)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212-4737
      • Allegheny General Hospital ( Site 1088)
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center ( Site 1089)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital ( Site 1039)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina ( Site 1003)
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • Statcare Pulmonary Consultants ( Site 1031)
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center ( Site 1079)
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus ( Site 1078)
    • Richmond, Virginia, United States, 23230
      • Pulmonary Associates of Richmond - West Broad Street ( Site 1069)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

- Completed sotatercept parent study (MK-7962-007[CADENCE] [Visit 9 and EOT visit] or MK-7962-041 [P041] [EOT Visit]) without discontinuing study intervention and is able to safely enroll into MK-7962-023 (HARMONIZE)

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has a diagnosis of pulmonary hypertension (PH) in world health organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
• Has had a study intervention interruption and has an ongoing SAE that occurred during parent study and is suspected to be related to study intervention
• Is pregnant or breastfeeding
• Has chronic liver disease with severe hepatic impairment and/or cirrhosis (eg, hepatic encephalopathy)
• Anticipation of more than 1 valve replacement or repair (mechanical or biomechanical) and/or have undergone more than 1 valve replacement or repair
• Has severe tricuspid regurgitation due to primary valvular disease (eg, from endocarditis, carcinoid, or mechanical destruction)
• Anticipated or undergone heart transplant or ventricular assist device implantation
• Has had prior exposure to luspatercept

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotatercept 0.3 mg/kg; Participants receive sotatercept 0.3 mg/kg subcutaneous (SC) injection every 3 weeks (Q3W) for up to approximately 10 years or until discontinuation.	Biological: Sotatercept; subcutaneous injection; Other Names: ACE-011
Experimental: Sotatercept 0.7 mg/kg; Participants receive sotatercept 0.7 mg/kg SC injection Q3W for up to approximately 10 years or until discontinuation.	Biological: Sotatercept; subcutaneous injection; Other Names: ACE-011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.	Up to approximately 10 years
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Parent Study Baseline in Pulmonary Vascular Resistance (PVR) at 6 Months Following Enrollment in the Extension	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization (RHC). The change from baseline in PVR at Month 6 will be presented. Per protocol, baseline was defined as the baseline data collected for each participant at the time of their enrollment on one of the parent studies.	Baseline and Month 6
Change From Baseline in the 6-Minute Walk Distance (6MWD) at 6 Months Following Enrollment in the Extension	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 6 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 6
Change From Baseline in the 6MWD at 12 Months Following Enrollment in the Extension	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 12 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 12
Change From Baseline in the 6MWD at 18 Months Following Enrollment in the Extension	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 18 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 18
Change From Baseline in the 6MWD at End of Treatment	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at the time of treatment discontinuation will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and up to approximately 43.5 months
Change From Baseline in New York Heart Association Functional Class (NYHA FC) at 6 Months Following Enrollment in the Extension	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 6 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 6
Change From Baseline in NYHA FC at 12 Months Following Enrollment in the Extension	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 12 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 12
Change From Baseline in NYHA FC at 18 Months Following Enrollment in the Extension	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 18 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 18
Change From Baseline in NYHA FC at End of Treatment	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at the time of treatment discontinuation will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and up to approximately 10 years
Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) at 6 Months Following Enrollment in the Extension	NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. The change from baseline in NT-proBNP at Month 6 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 6
Change From Baseline in NT-proBNP at 12 Months Following Enrollment in the Extension	NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. The change from baseline in NT-proBNP at Month 12 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 12
Change From Baseline in NT-proBNP at 18 Months Following Enrollment in the Extension	NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. The change from baseline in NT-proBNP at Month 18 will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and Month 18
Change From Baseline in NT-proBNP at End of Treatment	NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. The change from baseline in NT-proBNP at the time of treatment discontinuation will be presented. Per protocol, baseline may be either parent study baseline or the time of enrollment on this extension.	Baseline and up to approximately 10 years
Change From Parent Study Week 24 in PVR at 6 Months Following Enrollment in the Extension for Placebo Participants	PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization (RHC). The change from parent study Week 24 in PVR at Month 6 will be presented. Per protocol, baseline was defined as the value collected at Week 24 of the parent study.	Baseline and Month 6
Change From Baseline in 6MWD at 6 Months Following Enrollment in the Extension for Placebo Participants	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 6 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 6
Change From Baseline in 6MWD at 12 Months Following Enrollment in the Extension for Placebo Participants	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 12 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 12
Change From Baseline in 6MWD at 18 Months Following Enrollment in the Extension for Placebo Participants	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at Month 18 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 18
Change From Baseline in 6MWD at End of Treatment for Placebo Participants	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. The change from baseline in 6MWD at the time of treatment discontinuation will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and up to approximately 43.5 months
Change From Baseline in NYHA FC at 6 Months Following Enrollment in the Extension for Placebo Participants	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 6 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 6
Change From Baseline in NYHA FC at 12 Months Following Enrollment in the Extension for Placebo Participants	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 12 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 12
Change From Baseline in NYHA FC at 18 Months Following Enrollment in the Extension for Placebo Participants	NYHA FC classifies the extent of heart failure. The change from baseline in NYHA FC at Month 18 will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and Month 18
Change From Baseline in NYHA FC at End of Treatment for Placebo Participants	NYHA FC classifies the extent of heart failure. The change from extension baseline in NYHA FC at the time of treatment discontinuation will be presented. Per protocol, extension baseline was defined as the time of enrollment in the extension.	Baseline and up to approximately 10 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Estimated): August 10, 2035
• Study Completion (Estimated): August 10, 2035

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; ACE-011
• Other Study ID Numbers: 7962-023; MK-7962-023 (Other Identifier: MSD); U1111-1309-2142 (Registry Identifier: UTN); 2024-515773-99-00 (Registry Identifier: EU CT)

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