A Study of Sotatercept for the Treatment of Cpc-PH Due to HFpEF (MK-7962-007/A011-16)
Study Purpose
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).
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years - 85 Years |
Gender | All |
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.
- III. 5.
- - 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.
- - 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.
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. Documented significant 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.
- - 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.
- - 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.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04945460 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Medical Director |
Principal Investigator Affiliation | Merck Sharp & Dohme LLC |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Recruiting |
Countries | Belgium, Canada, France, Germany, Israel, Italy, Poland, Spain, Sweden, United Kingdom, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Hypertension, Pulmonary |
Study Website: | View Trial Website |
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.
Arms
Placebo Comparator: Placebo
Delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks in the placebo-controlled treatment period. After completion of the placebo-controlled treatment period, placebo participants will enter into 1 of the 2 sotatercept dose groups in an extension period.
Experimental: Sotatercept 0.3 mg/kg
Participants will receive sotatercept SC at a dose level of 0.3 mg/kg Q3W for 24 weeks in the placebo-controlled treatment period. After completion of the placebo-controlled treatment period, participants will continue to receive sotatercept SC at a dose level of 0.3 mg/kg Q3W in an extension period for up to 18 months.
Experimental: Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg
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.
Experimental: Extension Period: Placebo Crossed Over to Sotatercept 0.3 mg/kg
After the placebo-controlled treatment period, placebo participants will cross over to receive sotatercept SC at a dose of 0.3 mg/kg Q3W for up to 18 months in an extension period.
Experimental: Extension Period: Placebo Crossed Over to Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg
After the placebo-controlled treatment period, placebo participants will cross over to receive 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 then Q3W for up to 18 months in an extension period.
Interventions
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.
Drug: - Placebo
Administered by subcutaneous injection
Drug: - 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.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
PULMONARY ASSOCIATES, P.A. ( Site 1008)
Phoenix, Arizona, 85032
Status
Recruiting
Address
Cedars Sinai Medical Center ( Site 1082)
Los Angeles, California, 90048
Status
Recruiting
Address
University of California Irvine ( Site 1086)
Orange, California, 92868
Status
Recruiting
Address
Jeffrey S.Sager MD Medical Corporation ( Site 1060)
Santa Barbara, California, 93105-5311
Status
Active, not recruiting
Address
Stanford University ( Site 1024)
Stanford, California, 94305
Status
Recruiting
Address
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)
Torrance, California, 90502
Status
Recruiting
Address
University Of Colorado ( Site 1013)
Aurora, Colorado, 80045
Status
Recruiting
Address
South Denver Cardiology Associates ( Site 1091)
Littleton, Colorado, 80120
Status
Recruiting
Address
Winchester Chest Clinic ( Site 1093)
New Haven, Connecticut, 06519-1304
Status
Recruiting
Address
The George Washington University Medical Faculty Associates ( Site 1025)
Washington, District of Columbia, 20037-3201
Status
Recruiting
Address
Bay Area Cardiology ( Site 1071)
Brandon, Florida, 33511
Status
Recruiting
Address
Mayo Clinic Jacksonville - PPDS ( Site 1045)
Jacksonville, Florida, 32224
Status
Recruiting
Address
AdventHealth Orlando ( Site 1058)
Orlando, Florida, 32803
Status
Recruiting
Address
Tampa General Hospital ( Site 1043)
Tampa, Florida, 33606
Status
Recruiting
Address
Piedmont Atlanta Hospital ( Site 1085)
Atlanta, Georgia, 30309-1281
Status
Recruiting
Address
Emory University ( Site 1030)
Atlanta, Georgia, 30322-1013
Status
Recruiting
Address
Saint Alphonsus Regional Medical Center ( Site 1097)
Boise, Idaho, 83704-8880
Status
Recruiting
Address
University of Illinois Hospital ( Site 1095)
Chicago, Illinois, 60612
Status
Recruiting
Address
IU Health Advanced Heart and Lung Care ( Site 1092)
Indianapolis, Indiana, 46202-1218
Status
Recruiting
Address
Ascension Medical Group St. Vincent ( Site 1076)
Indianapolis, Indiana, 46260
Status
Recruiting
Address
University of Iowa Hospital and Clinics ( Site 1050)
Iowa City, Iowa, 52242
Status
Recruiting
Address
University of Kansas Medical Center ( Site 1020)
Kansas City, Kansas, 66160
Status
Recruiting
Address
Norton Pulmonary Specialists ( Site 1066)
Louisville, Kentucky, 40202
Status
Recruiting
Address
University Medical Center New Orleans ( Site 1057)
New Orleans, Louisiana, 70112
Status
Recruiting
Address
Tufts Medical Center - PPDS ( Site 1012)
Boston, Massachusetts, 02111
Status
Recruiting
Address
Brigham and Women's Hospital [Boston, MA] ( Site 1014)
Boston, Massachusetts, 02215
Status
Recruiting
Address
University of Michigan ( Site 1011)
Ann Arbor, Michigan, 48109
Status
Completed
Address
University of Minnesota Hospitals ( Site 1062)
Minneapolis, Minnesota, 55455
Status
Recruiting
Address
Washington University School of Medicine [Saint Louis, MO] ( Site 1022)
Saint Louis, Missouri, 63110
Status
Recruiting
Address
University of Nebraska Medical Center ( Site 1053)
Omaha, Nebraska, 68198
Status
Recruiting
Address
Pulmonary Health Physicians ( Site 1080)
Liverpool, New York, 13088
Status
Recruiting
Address
Weill Cornell Medical College ( Site 1046)
New York, New York, 10021-9800
Status
Recruiting
Address
University of Rochester Medical Center - PPDS ( Site 1039)
Rochester, New York, 14642
Status
Recruiting
Address
The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)
Cincinnati, Ohio, 45219
Status
Recruiting
Address
University Hospitals Cleveland Medical Center ( Site 1005)
Cleveland, Ohio, 44106
Status
Recruiting
Address
Cleveland Clinic Foundation ( Site 1065)
Cleveland, Ohio, 44195
Status
Completed
Address
University of Toledo Medical Center ( Site 1070)
Toledo, Ohio, 43614
Status
Recruiting
Address
Oregon Health Science University ( Site 1054)
Portland, Oregon, 97239-3098
Status
Recruiting
Address
Allegheny General Hospital ( Site 1088)
Pittsburgh, Pennsylvania, 15212-4737
Status
Recruiting
Address
Lankenau Institute for Medical Research ( Site 1089)
Wynnewood, Pennsylvania, 19096
Status
Recruiting
Address
Rhode Island Hospital ( Site 1033)
East Providence, Rhode Island, 02915
Status
Recruiting
Address
Medical University of South Carolina - PPDS ( Site 1003)
Charleston, South Carolina, 29425-0001
Status
Recruiting
Address
Statcare Pulmonary Consultants - Knoxville ( Site 1031)
Knoxville, Tennessee, 37919
Status
Recruiting
Address
Intermountain Medical Center ( Site 1079)
Murray, Utah, 84107
Status
Recruiting
Address
Inova Heart and Vascular Institute ( Site 1078)
Falls Church, Virginia, 22042
Status
Recruiting
Address
Bon Secours St. Mary's Hospital ( Site 1069)
Richmond, Virginia, 23226
Status
Active, not recruiting
Address
West Virginia University ( Site 1081)
Morgantown, West Virginia, 26506
Status
Recruiting
Address
Aurora St Luke's Medical Center ( Site 1083)
Milwaukee, Wisconsin, 53215
Status
Recruiting
Address
Froedtert Hospital & the Medical College of Wisconsin ( Site 1051)
Milwaukee, Wisconsin, 53226
International Sites
Status
Recruiting
Address
Hôpital Erasme ( Site 1402)
Anderlecht, Bruxelles-Capitale, Region De, 1070
Status
Recruiting
Address
UZ Leuven - Campus Gasthuisberg ( Site 1401)
Leuven, Vlaams-Brabant, 3000
Status
Recruiting
Address
University Of Alberta ( Site 2101)
Edmonton, Alberta, T6G 2B7
Status
Recruiting
Address
Hamilton General Hospital-Special Immunology Services Clinic ( Site 2110)
Hamilton, Ontario, L8L 2X2
Status
Recruiting
Address
Institut Universitaire de Cardiologie et de Pneumologie ( Site 2107)
Sainte Foy, Quebec, G1V 4G5
Status
Recruiting
Address
Hôpital Pasteur - CHU Nice ( Site 1311)
Nice, Alpes-Maritimes, 06000
Status
Recruiting
Address
Centre Hospitalier Universitaire du Besancon ( Site 1324)
Besançon, Doubs, 25000
Status
Recruiting
Address
Hopital de Rangueil du Toulouse ( Site 1322)
Toulouse, Haute-Garonne, 31400
Status
Recruiting
Address
CHU Montpellier Hôpital Arnaud de VIlleneuve ( Site 1301)
Montpellier, Herault, 34090
Status
Recruiting
Address
Hôpital Pontchaillou ( Site 1319)
Rennes, Ille-et-Vilaine, 35033
Status
Recruiting
Address
Centre Hospitalier Universitaire de Grenoble ( Site 1303)
Grenoble cedex 09, Isere, 38043
Status
Recruiting
Address
CHU de Nantes - Hoptal Nord Laennec ( Site 1309)
Nantes, Loire-Atlantique, 44093
Status
Recruiting
Address
CHU Angers ( Site 1313)
Angers, Maine-et-Loire, 49933
Status
Recruiting
Address
CHRU de Nancy Hopitaux de Brabois ( Site 1308)
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54500
Status
Recruiting
Address
CHRU Lille ( Site 1306)
Lille, Nord, 59037
Status
Recruiting
Address
CHU de Rouen ( Site 1323)
Rouen, Seine-Maritime, 76000
Status
Recruiting
Address
Centre Hospitalier Universitaire de Bicetre ( Site 1304)
Le Kremlin Bicêtre, Val-de-Marne, 94270
Status
Recruiting
Address
Thoraxklinik-Heidelberg gGmbH ( Site 1509)
Heidelberg, Baden-Wurttemberg, 69126
Status
Recruiting
Address
Krankenhaus Neuwittelsbach ( Site 1510)
München, Bayern, 80639
Status
Recruiting
Address
University Hospital Regensburg ( Site 1503)
Regensburg, Bayern, 93053
Status
Recruiting
Address
Kerckhoff-Klinik-Forschungs-GmbH ( Site 1514)
Bad Nauheim, Hessen, 61231
Status
Recruiting
Address
Universitätsklinikum Gießen und Marburg GmbH ( Site 1512)
Gießen, Hessen, 35392
Status
Recruiting
Address
Universitaetsmedizin Johannes Gutenberg Universitaet Mainz ( Site 1515)
Mainz, Rheinland-Pfalz, 55131
Status
Recruiting
Address
Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)
Dresden, Sachsen, 01307
Status
Recruiting
Address
Assuta Ashdod Medical Center ( Site 1710)
Ashdod, , 7747629
Status
Recruiting
Address
Shamir Medical Center Assaf Harofeh ( Site 1713)
Be'er Ya'akov, , 7030001
Status
Recruiting
Address
Rambam Health Corp. ( Site 1716)
Haifa, , 3109601
Status
Recruiting
Address
Lady Davis Carmel Medical Center ( Site 1705)
Haifa, , 34362
Status
Recruiting
Address
Edith Wolfson Medical Center ( Site 1717)
Holon, , 58100
Status
Recruiting
Address
Hadassah Ein Kerem Medical Center ( Site 1711)
Jerusalem, , 9574425
Status
Recruiting
Address
Rabin Medical Center ( Site 1703)
Petah Tiqwa, , 4941492
Status
Recruiting
Address
Kaplan Medical Center ( Site 1712)
Rehovot, , 7610001
Status
Recruiting
Address
ZIV Medical Center ( Site 1704)
Safed, , 13100
Status
Recruiting
Address
Tel Aviv Sourasky Medical Center ( Site 1714)
Tel Aviv, , 64239
Status
Recruiting
Address
AOU di Bologna Policlinico S Orsola Malpighi ( Site 2409)
Bologna, Emilia-Romagna, 40138
Status
Recruiting
Address
Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)
Trieste, Friuli-Venezia Giulia, 34149
Status
Recruiting
Address
Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo ( Site 2406)
Monza, Lombardia, 20900
Status
Recruiting
Address
Fondazione IRCCS-Policlinico San Matteo ( Site 2401)
Pavia, Lombardia, 27100
Status
Recruiting
Address
Ospedale SS Annunziata ( Site 2408)
Sassari, Sardegna, 07100
Status
Recruiting
Address
ASST Papa Giovanni XXIII ( Site 2410)
Bergamo, , 24127
Status
Recruiting
Address
Azienda Policlinico Umberto I ( Site 2402)
Roma, , 00161
Status
Recruiting
Address
Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 2806)
Lubin, Lubelskie, 20-718
Status
Recruiting
Address
Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2801)
Krakow, Malopolskie, 31-202
Status
Recruiting
Address
Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)
Otwock, Mazowieckie, 05-400
Status
Recruiting
Address
Państwowy Instytut Medyczny MSWiA ( Site 2805)
Warszawa, Mazowieckie, 02-507
Status
Recruiting
Address
Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)
Majadahonda, Madrid, 28222
Status
Recruiting
Address
Hospital Clinic de Barcelona ( Site 1602)
Barcelona, , 08036
Status
Recruiting
Address
Hospital Universitario 12 de Octubre ( Site 1603)
Madrid, , 28041
Status
Recruiting
Address
Hospital Universitario Virgen Macarena ( Site 1612)
Sevilla, , 41009
Status
Recruiting
Address
Hospital Universitario de Toledo ( Site 1607)
Toledo, , 41007
Status
Recruiting
Address
Sahlgrenska Universitetssjukhuset ( Site 3201)
Goteburg, Vastra Gotalands Lan, 413 45
Status
Recruiting
Address
Imperial College Healthcare NHS Trust ( Site 1203)
London, London, City Of, W12 0HS