Hypertension, PulmonaryPhase 2CADENCENCT04945460
A Study of Sotatercept for the Treatment of Cpc-PH Due to HFpEF (MK-7962-007/A011-16)
A Phase 2 study testing Sotatercept 0.3 mg/kg and Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg in people with Hypertension, Pulmonary, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 119 sites in 12 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- Sotatercept 0.3 mg/kg and Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 119 sitesin 12 countries
- Study dates
- 29 Dec 2021to 9 Apr 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- 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
- Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
- Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
- Ability to understand and provide documented consent for participation
Who cannot join
- 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)
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- 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
- Hospitalization for any worsening of medical conditions or any significant surgery per investigator within 30 days of Visit 1
- 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
- Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin, or levosimendan) within 30 days of Visit 1
- Received erythropoietin within 6 months of Visit 1
- 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)
- Prior exposure to sotatercept or luspatercept
- 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
- 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)
- 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
- History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
- Major surgery within 60 days of Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1
- Prior organ transplantation (e.g., heart, lung, liver, kidney), bone marrow transplantation, or life expectancy of < 12 months
- Pregnancy or breastfeeding in females
- 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
- 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
- Body mass index ≥50 kg/m2
- More than mild obstructive sleep apnea (treated or untreated)
- Any non-cardiopulmonary condition or acute/chronic impairment(s) (other than dyspnea) that limits the ability to perform 6-minute walk test (6MWT)
Trial locations and contacts
119 sites in 12 countries.
119 sites in 12 countries
United States56 sites
University of Michigan ( Site 1011)
Ann Arbor, Michigan, 48109
Piedmont Atlanta Hospital ( Site 1085)
Atlanta, Georgia, 30309-1281
Emory University ( Site 1030)
Atlanta, Georgia, 30322-1013
University Of Colorado ( Site 1013)
Aurora, Colorado, 80045
Saint Alphonsus Regional Medical Center ( Site 1097)
Boise, Idaho, 83704-8880
Tufts Medical Center - PPDS ( Site 1012)
Boston, Massachusetts, 02111
Brigham and Women's Hospital [Boston, MA] ( Site 1014)
Boston, Massachusetts, 02115
Bay Area Cardiology ( Site 1071)
Brandon, Florida, 33511
Medical University of South Carolina - PPDS ( Site 1003)
Charleston, South Carolina, 29425-0001
University of Illinois Hospital ( Site 1095)
Chicago, Illinois, 60612
The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)
Cincinnati, Ohio, 45219
University Hospitals Cleveland Medical Center ( Site 1005)
Cleveland, Ohio, 44106
Cleveland Clinic Foundation ( Site 1065)
Cleveland, Ohio, 44195
The Ohio State University Wexner Medical Center ( Site 1032)
Columbus, Ohio, 43210
Baylor University Medical Center ( Site 1096)
Dallas, Texas, 75246
University of Texas Southwestern Medical Center ( Site 4002)
Dallas, Texas, 75390
Duke University Medical Center ( Site 1026)
Durham, North Carolina, 27710-4000
Inova Heart and Vascular Institute ( Site 1078)
Falls Church, Virginia, 22042
IU Health Advanced Heart and Lung Care ( Site 1092)
Indianapolis, Indiana, 46202-1218
Ascension Medical Group St. Vincent ( Site 1076)
Indianapolis, Indiana, 46260
University of Iowa Hospital and Clinics ( Site 1050)
Iowa City, Iowa, 52242
Mayo Clinic Jacksonville - PPDS ( Site 1045)
Jacksonville, Florida, 32224
University of Kansas Medical Center ( Site 1020)
Kansas City, Kansas, 66160
Statcare Pulmonary Consultants - Knoxville ( Site 1031)
Knoxville, Tennessee, 37919
Scripps Clinic ( Site 4001)
La Jolla, California, 92037-1205
South Denver Cardiology Associates ( Site 1091)
Littleton, Colorado, 80120
Pulmonary Health Physicians ( Site 1080)
Liverpool, New York, 13088
Cedars Sinai Medical Center ( Site 1082)
Los Angeles, California, 90048
Norton Pulmonary Specialists ( Site 1066)
Louisville, Kentucky, 40202
University of Louisville ( Site 1099)
Louisville, Kentucky, 40202
Aurora St Luke's Medical Center ( Site 1083)
Milwaukee, Wisconsin, 53215
Froedtert Hospital & the Medical College of Wisconsin ( Site 1051)
Milwaukee, Wisconsin, 53226
University of Minnesota Hospitals ( Site 1062)
Minneapolis, Minnesota, 55455
West Virginia University ( Site 1081)
Morgantown, West Virginia, 26506
Intermountain Medical Center ( Site 1079)
Murray, Utah, 84107
Winchester Chest Clinic ( Site 1093)
New Haven, Connecticut, 06519-1304
University Medical Center New Orleans ( Site 1057)
New Orleans, Louisiana, 70112
Weill Cornell Medical College ( Site 1046)
New York, New York, 10021-9800
University of Nebraska Medical Center ( Site 1053)
Omaha, Nebraska, 68198
University of California Irvine ( Site 1086)
Orange, California, 92868
AdventHealth Orlando ( Site 1058)
Orlando, Florida, 32803
PULMONARY ASSOCIATES, P.A. ( Site 1008)
Phoenix, Arizona, 85032
Allegheny General Hospital ( Site 1088)
Pittsburgh, Pennsylvania, 15212-4737
Oregon Health Science University ( Site 1054)
Portland, Oregon, 97126
Rhode Island Hospital ( Site 1033)
Providence, Rhode Island, 02903
Bon Secours St. Mary's Hospital ( Site 1069)
Richmond, Virginia, 23226
University of Rochester Medical Center - PPDS ( Site 1039)
Rochester, New York, 14642
Jeffrey S.Sager MD Medical Corporation ( Site 1060)
Santa Barbara, California, 93105-5311
Washington University School of Medicine [Saint Louis, MO] ( Site 1022)
St Louis, Missouri, 63110
Stanford University ( Site 1024)
Stanford, California, 94305
Tampa General Hospital ( Site 1043)
Tampa, Florida, 33606
University of Toledo Medical Center ( Site 1070)
Toledo, Ohio, 43614
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)
Torrance, California, 90502
University of Arizona ( Site 1006)
Tucson, Arizona, 85724-0001
The George Washington University Medical Faculty Associates ( Site 1025)
Washington D.C., District of Columbia, 20037-3201
Lankenau Institute for Medical Research ( Site 1089)
Wynnewood, Pennsylvania, 19096
France12 sites
CHU Angers ( Site 1313)
Angers, Maine-et-Loire, 49933
Centre Hospitalier Universitaire du Besancon ( Site 1324)
Besançon, Doubs, 25000
Centre Hospitalier Universitaire de Grenoble ( Site 1303)
Grenoble, Isere, 38043
Centre Hospitalier Universitaire de Bicetre ( Site 1304)
Le Kremlin-Bicêtre, Val-de-Marne, 94270
CHRU Lille ( Site 1306)
Lille, Nord, 59037
CHU Montpellier Hôpital Arnaud de VIlleneuve ( Site 1301)
Montpellier, Herault, 34090
CHU de Nantes - Hoptal Nord Laennec ( Site 1309)
Nantes, Loire-Atlantique, 44000
Hôpital Pasteur - CHU Nice ( Site 1311)
Nice, Alpes-Maritimes, 06000
Hôpital Pontchaillou ( Site 1319)
Rennes, Ille-et-Vilaine, 35033
CHU de Rouen ( Site 1323)
Rouen, Seine-Maritime, 76000
Hopital de Rangueil du Toulouse ( Site 1322)
Toulouse, Haute-Garonne, 31400
CHRU de Nancy Hopitaux de Brabois ( Site 1308)
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54500
Israel12 sites
Assuta Ashdod Medical Center ( Site 1710)
Ashdod, 7747629
Shamir Medical Center Assaf Harofeh ( Site 1713)
Be’er Ya‘aqov, 70300
Rambam Health Corp. ( Site 1716)
Haifa, 3109601
Lady Davis Carmel Medical Center ( Site 1705)
Haifa, 3436212
Edith Wolfson Medical Center ( Site 1717)
Holon, 5810001
Shaare Zedek Medical Center ( Site 1715)
Jerusalem, 91031
Hadassah Ein Kerem Medical Center ( Site 1711)
Jerusalem, 91120
Meir Medical Center. ( Site 1707)
Kfar Saba, 4428164
Rabin Medical Center ( Site 1703)
Petah Tikva, 4941492
Kaplan Medical Center ( Site 1712)
Rehovot, 7610001
ZIV Medical Center ( Site 1704)
Safed, 13100
Tel Aviv Sourasky Medical Center ( Site 1714)
Tel Aviv, 64239
Germany10 sites
Kerckhoff-Klinik-Forschungs-GmbH ( Site 1514)
Bad Nauheim, Hesse, 61231
DRK Kliniken Berlin Westend ( Site 1507)
Berlin, 14050
Uniklinik Köln ( Site 1511)
Cologne, North Rhine-Westphalia, 50931
Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)
Dresden, Saxony, 01307
Universitätsklinikum Gießen und Marburg GmbH ( Site 1512)
Giessen, Hesse, 35392
Medizinische Hochschule Hannover ( Site 1505)
Hanover, Lower Saxony, 30625
Thoraxklinik-Heidelberg gGmbH ( Site 1509)
Heidelberg, Baden-Wurttemberg, 69126
Universitaetsmedizin Johannes Gutenberg Universitaet Mainz ( Site 1515)
Mainz, Rhineland-Palatinate, 55131
Krankenhaus Neuwittelsbach ( Site 1510)
München, Bavaria, 80639
University Hospital Regensburg ( Site 1503)
Regensburg, Bavaria, 93053
Italy7 sites
ASST Papa Giovanni XXIII ( Site 2410)
Bergamo, 24127
AOU di Bologna Policlinico S Orsola Malpighi ( Site 2409)
Bologna, Emilia-Romagna, 40138
Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo ( Site 2406)
Monza, Lombardy, 20900
Fondazione IRCCS-Policlinico San Matteo ( Site 2401)
Pavia, Lombardy, 27100
Azienda Policlinico Umberto I ( Site 2402)
Roma, 00161
Ospedale SS Annunziata ( Site 2408)
Sassari, Sardinia, 07100
Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)
Trieste, Friuli Venezia Giulia, 34149
Poland7 sites
Uniwersytecki Szpital Kliniczny w Bialymstoku - Marii Sklodowskiej-Curie 24A ( Site 2803)
Bialystok, Podlaskie Voivodeship, 15-276
Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2801)
Krakow, Lesser Poland Voivodeship, 31-202
Wojewodzki Specjalistyczny Szpital im dr WI Bieganskiego w Lodzi ( Site 2807)
Lodz, Łódź Voivodeship, 91-347
Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 2806)
Lubin, Lublin Voivodeship, 20-718
Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)
Otwock, Masovian Voivodeship, 05-400
Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie ( Site 2804)
Szczecin, West Pomeranian Voivodeship, 70-111
Państwowy Instytut Medyczny MSWiA ( Site 2805)
Warsaw, Masovian Voivodeship, 02-507
Spain6 sites
Hospital Clinic de Barcelona ( Site 1602)
Barcelona, 08036
Hospital Universitario 12 de Octubre ( Site 1603)
Madrid, 28041
Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)
Majadahonda, Madrid, 28222
Hospital Costa del Sol ( Site 1613)
Marbella, Malaga, 29603
Hospital Universitario Virgen Macarena ( Site 1612)
Seville, 41009
Hospital Universitario de Toledo ( Site 1607)
Toledo, 41007
Canada4 sites
University Of Alberta ( Site 2101)
Edmonton, Alberta, T6G 2B7
Hamilton General Hospital-Special Immunology Services Clinic ( Site 2110)
Hamilton, Ontario, L8L 2X2
Institut Universitaire de Cardiologie et de Pneumologie ( Site 2107)
Sainte-Foy, Quebec, G1V 4G5
University Health Network ( Site 2109)
Toronto, Ontario, M5G 2N2
Belgium2 sites
Hôpital Erasme ( Site 1402)
Anderlecht, Bruxelles-Capitale, Region de, 1070
UZ Leuven - Campus Gasthuisberg ( Site 1401)
Leuven, Vlaams-Brabant, 3000
Mexico1 site
Unidad de Investigacion Clinica En Medicina SC ( Site 2505)
Monterrey, Nuevo León, 64710
Sweden1 site
Sahlgrenska Universitetssjukhuset ( Site 3201)
Gothenburg, Västra Götaland County, 413 45
United Kingdom1 site
Imperial College Healthcare NHS Trust ( Site 1203)
London, London, City of, W12 0HS
About this study
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)
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).
Read the detailed 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.
As of protocol amendment 6, the 18-month Extension Period is being removed. Participants who have completed at least the 24-week placebo controlled treatment period and the end of study visit, and who have not discontinued study treatment early, may be eligible to participate in an extension study.
- Conditions
- Hypertension, Pulmonary
- Being tested
- Sotatercept 0.3 mg/kg, Placebo, Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg
- Keywords
- Pulmonary, hypertension, Cpc PH, HFpEF, sotatercept
- Medical subject headings
- Hypertension, Pulmonary, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sotatercept 0.3 mg/kgDrug
Also called ACE-011
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.
PlaceboDrug
Administered by subcutaneous injection
Sotatercept 0.3 mg/kg escalating to 0.7 mg/kgDrug
Also called ACE-011
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks in the placebo-controlled treatment period. Receives: 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. Receives: 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. Receives: Drug: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
PVR, a hemodynamic variable of pulmonary circulation, was measured by right heart catheterization (RHC). Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Secondary outcomes (15)
Base Study: Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 24
The 6MWD was performed to assess functional capacity. The 6MWD was assessed using the 6-minute walk test (6MWT) to measure the distance covered over a time period of 6 minutes. An increase in the distance walked during the 6MWT indicated improvement in functional exercise capacity. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: Time to First Clinical Worsening Event (TTCW) at Weeks 24
Clinical Worsening events were 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 4hours, but no more than 1 week apart.
Measured: 24 Weeks
Base Study: Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24
mPAP was calculated from systolic and diastolic pulmonary artery pressure measured by right heart catheterization. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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 was used as an indicator of diastolic dysfunction. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: Change From Baseline in Ratio of Mitral Inflow Velocity E to Mitral Annular Velocity'(e') (E/e' Ratio) at Week 24
E/e' is a ratio of mitral inflow velocity E to mitral annular velocity (e') as measured by electrocardiography as an indicator of diastolic function. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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 of the peak velocity flow of the E wave in the early diastole to peak velocity flow of the A wave in late diastole measured by echocardiography as an indicator of diastolic function. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: 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. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: Change From Baseline in New York Heart Association Functional Class (NYHA FC) at Week 24
NYHA FC classified the extent of heart failure (HF). Participant HF symptoms were graded using the NYHA FC system. NYHA FC for HF ranges from Class I (no limitation of physical activity, or ordinary physical activity does not cause undue fatigue, palpitation, dyspnea [shortness of breath]), Class II (slight limitation of physical activity, comfortable at rest, or ordinary physical activity results in fatigue, palpitation, dyspnea [shortness of breath]), Class III (marked limitation of physical activity, comfortable at rest, or less than ordinary activity causes fatigue, palpitation, or dyspnea) and Class IV (unable to carry on any physical activity without discomfort, symptoms of HF at rest or if any physical activity is undertaken, discomfort increases). Participants were classified as "Improved or Maintained" or "Not Improved nor Not Maintained". Improved or Maintained = reduction in NYHA FC or no change in NYHA FC; Not Improved nor Not Maintained = increase in NYHA FC.
Measured: Baseline and Week 24
Base Study: Change From Baseline in Myocardial Contraction Fraction (MCF) at Week 24
MCF is an echocardiographic measurement that determined the ratio of left ventricular stroke volume to myocardial volume and was an indicator of left ventricular systolic function. Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Measured: Baseline and Week 24
Base Study: Number of Participants With One or More Adverse Events (AEs)
An AE was defined as 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 experienced an AE was reported.
Measured: Up to approximately 6 months
Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as 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 experienced an AE was reported.
Measured: Up to approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start29 Dec 2021
- Primary completion5 Sep 2025
- Study completion9 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04945460
- Sponsor's protocol ID
- 7962-007
- Other IDs
- A011-16, MK-7962-007, 2023-509141-12-00, U1111-1309-6433, 2021-003020-32, 2023
- Acronym
- CADENCE
- Status last verified
- Aug 2026
- First submitted
- 11 Jun 2021
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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 Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study. Circulation. 2026 May 12;153(19):1446-1459. doi: 10.1161/CIRCULATIONAHA.126.079918. Epub 2026 Mar 29.
PubMed 41904795