Clinical trial NCT04945460: A Study of Sotatercept for the Treatment of Cpc-PH Due to HFpEF (MK-7962-007/A011-16)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary, hypertension, Cpc PH, HFpEF, sotatercept
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: Inclusion Criteria:

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

1. Age 18 to 85 years
2. Clinical diagnosis of HFpEF:

   • Left ventricular ejection fraction ≥50%, with no history of LVEF below 45% in more than two consecutive measurements under stable conditions
3. Demonstrated Cpc-PH by all of the following:

   * Baseline RHC performed within 28 days of randomization documenting a minimum PVR of ≥320 dyn•sec/cm5 (4 wood units)
   * Mean pulmonary arterial pressure (mPAP) of \>20 mmHg
   * Pulmonary capillary wedge pressure (PCWP) \>15 mmHg but \< 30 mmHg
4. New York Heart Association FC of II or III
5. Six-minute Walk Distance ≥100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value
6. Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for ≥30 days prior to Visit 1. Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within 30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1. Anticoagulation may be suspended for RHC if necessary.
7. Women of childbearing potential must:

   * Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
   * If sexually active with a male partner: use highly effective contraception without interruption for at least 28 days prior to starting the investigational product AND agree to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment
   * Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug
8. Male participants must:

   * Agree to use a condom, defined as a male latex condom or non latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
   * Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug
9. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
10. Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
11. Ability to understand and provide documented consent for participation

Exclusion Criteria:

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

1. A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
2. Clinically significant and active lung disease:

   * Chronic obstructive pulmonary disease with post-bronchodilator forced expiratory volume in the first second (FEV1) \<60% predicted
   * Restrictive lung disease with total lung capacity \<70% predicted
   * More than mild interstitial lung disease (ILD), with FVC\<70% or FEV1\<60% predicted (still appropriate if absence of more than mild ILD, fibrosis, or COPD on computed tomography \[CT\] imaging)
3. Cardiovascular co-morbidities, which include any of the following:

   * History of more than mild mitral or aortic stenosis
   * Ongoing more than mild mitral or aortic regurgitation
   * More than one valve replacement or repair (mechanical or biomechanical) or anticipation of any valve replacement or repair
   * Severe tricuspid regurgitation due to primary valvular disease
   * Occurrence of myocardial infarction, acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1
   * History of serious life-threatening or hemodynamically significant arrhythmia
   * History of or anticipated heart transplant or ventricular assist device implantation
   * History of implantable cardioverter defibrillator placement or anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening
   * Anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening or history of implantable cardioverter defibrillator placement
   * Occurrence of myocardial infarction within 180 days of Visit 1
   * History of known pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy
   * Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \>160 mmHg or sitting diastolic blood pressure \>110 mmHg during Screening after a period of rest
   * Systemic hypotension as evidenced by sitting systolic blood pressure \<90 mmHg or sitting diastolic blood pressure \<50 mmHg during Screening
   * Resting heart rate of \<45 bpm or \>115 bpm
   * Stroke within 90 days of Visit 1
   * Acutely decompensated HF that required hospitalization within 30 days of Visit 1
   * Electrocardiogram during Screening Period with Fridericia's corrected QT interval (QTcF) \>470 msec for males or \>480 msec for females, or \>500 msec if a ventricular conduction defect (right bundle branch block; left bundle branch block; or interventricular conduction delay) is present
   * Personal or family history of Brugada syndrome, sudden cardiac arrest or unexplained sudden cardiac death or arrest
   * Personal or family history of long QT syndrome unless the participant's ECG shows a normal QTc
   * Arrhythmogenic right ventricular dysplasia (ARVD) unless the participant has a recent cardiac MRI that shows no evidence of this diagnosis
4. Hospitalization for any worsening of medical conditions or any significant surgery per investigator within 30 days of Visit 1.
5. Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators) within 30 days of Visit 1.The use of an oral phosphodiesterase type 5 inhibitor, if only indicated for erectile dysfunction, is permitted, if not administered within 48 hours of a study visit or procedure.
6. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin,or levosimendan) within 30 days of Visit 1
7. Received erythropoietin within 6 months of Visit 1.
8. Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), with severe hepatic impairment and/or cirrhosis (e.g., hepatic encephalopathy)
9. Prior exposure to sotatercept or luspatercept.
10. Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented consent.
11. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days of Visit 1 or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
12. Any of the following clinical laboratory values prior to Visit 1 as specified:

    * Hemoglobin (Hgb) above the gender-specific upper limit of normal (ULN) per local laboratory test within 28 days of Visit 1or \<10 g/dL per local laboratory within 28 days of Visit 1
    * Serum alanine aminotransferase or aspartate aminotransferase levels \>3× ULN or total bilirubin \>3× ULN within 28 days of Visit 1
    * Estimated glomerular filtration rate \<30 ml/min/1.73 m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of Visit 1 or required renal replacement therapy within 90 days of Visit 1
    * Glycated hemoglobin (HbA1c) \>10% within 28 days of Visit 1
    * Platelet count \< 75,000/mm3 within 28 days of Visit 1
13. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product .
14. Major surgery within 60 days of Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1.
15. Prior organ transplantation (e.g., heart, lung, liver, kidney), bone marrow transplantation, or life expectancy of \< 12 months.
16. Pregnancy or breastfeeding in females.
17. Active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or ≤ 2 squamous cell carcinomas of the skin.
18. History of clinically significant (as determined by the investigator) endocrine, hematologic, hepatic, (auto)immune, infectious (requiring chronic antibiotics), metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study.
19. Body mass index ≥50 kg/m2.
20. More than mild obstructive sleep apnea (treated or untreated).
21. Any non-cardiopulmonary condition or acute/chronic impairment(s) (other than dyspnea) that limits the ability to perform 6-minute walk test (6MWT).

Primary outcomes:
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 24
timeFrame: Baseline and Week 24
measure: Time to First Clinical Worsening Event (TTCW) at Weeks 24
timeFrame: Week 24
measure: Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Right Ventricular Fractional Area Change (RVFAC) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in ratio of mitral inflow velocity I to mitral annular velocity'(e') (E/e' ratio) at Week 24
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Baseline and Week 24
measure: Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in New York Heart Association Functional Class (NYHA FC) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Myocardial Contraction Fraction (MCF) at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: PULMONARY ASSOCIATES, P.A. ( Site 1008)
state: Arizona
city: Tucson
country: United States
facility: University of Arizona ( Site 1006)
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic ( Site 4001)
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center ( Site 1082)
state: California
city: Orange
country: United States
facility: University of California Irvine ( Site 1086)
state: California
city: Santa Barbara
country: United States
facility: Jeffrey S.Sager MD Medical Corporation ( Site 1060)
state: California
city: Stanford
country: United States
facility: Stanford University ( Site 1024)
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)
state: California
city: Aurora
country: United States
facility: University Of Colorado ( Site 1013)
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology Associates ( Site 1091)
state: Colorado
city: New Haven
country: United States
facility: Winchester Chest Clinic ( Site 1093)
state: Connecticut
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates ( Site 1025)
state: District of Columbia
city: Brandon
country: United States
facility: Bay Area Cardiology ( Site 1071)
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS ( Site 1045)
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando ( Site 1058)
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital ( Site 1043)
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital ( Site 1085)
state: Georgia
city: Atlanta
country: United States
facility: Emory University ( Site 1030)
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center ( Site 1097)
state: Idaho
city: Chicago
country: United States
facility: University of Illinois Hospital ( Site 1095)
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Advanced Heart and Lung Care ( Site 1092)
state: Indiana
city: Indianapolis
country: United States
facility: Ascension Medical Group St. Vincent ( Site 1076)
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics ( Site 1050)
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 1020)
state: Kansas
city: Louisville
country: United States
facility: Norton Pulmonary Specialists ( Site 1066)
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville ( Site 1099)
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center New Orleans ( Site 1057)
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center - PPDS ( Site 1012)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital [Boston, MA] ( Site 1014)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 1011)
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Hospitals ( Site 1062)
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine [Saint Louis, MO] ( Site 1022)
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center ( Site 1053)
state: Nebraska
city: Liverpool
country: United States
facility: Pulmonary Health Physicians ( Site 1080)
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College ( Site 1046)
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - PPDS ( Site 1039)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center ( Site 1026)
state: North Carolina
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center ( Site 1005)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation ( Site 1065)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center ( Site 1032)
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center ( Site 1070)
state: Ohio
city: Portland
country: United States
facility: Oregon Health Science University ( Site 1054)
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital ( Site 1088)
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Institute for Medical Research ( Site 1089)
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital ( Site 1033)
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS ( Site 1003)
state: South Carolina
city: Knoxville
country: United States
facility: Statcare Pulmonary Consultants - Knoxville ( Site 1031)
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center ( Site 1096)
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center ( Site 4002)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center ( Site 1079)
state: Utah
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute ( Site 1078)
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital ( Site 1069)
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University ( Site 1081)
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St Luke's Medical Center ( Site 1083)
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin ( Site 1051)
state: Wisconsin
city: Anderlecht
country: Belgium
facility: Hôpital Erasme ( Site 1402)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg ( Site 1401)
state: Vlaams-Brabant
city: Edmonton
country: Canada
facility: University Of Alberta ( Site 2101)
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton General Hospital-Special Immunology Services Clinic ( Site 2110)
state: Ontario
city: Toronto
country: Canada
facility: University Health Network ( Site 2109)
state: Ontario
city: Sainte Foy
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie ( Site 2107)
state: Quebec
city: Nice
country: France
facility: Hôpital Pasteur - CHU Nice ( Site 1311)
state: Alpes-Maritimes
city: Besançon
country: France
facility: Centre Hospitalier Universitaire du Besancon ( Site 1324)
state: Doubs
city: Toulouse
country: France
facility: Hopital de Rangueil du Toulouse ( Site 1322)
state: Haute-Garonne
city: Montpellier
country: France
facility: CHU Montpellier Hôpital Arnaud de VIlleneuve ( Site 1301)
state: Herault
city: Rennes
country: France
facility: Hôpital Pontchaillou ( Site 1319)
state: Ille-et-Vilaine
city: Grenoble cedex 09
country: France
facility: Centre Hospitalier Universitaire de Grenoble ( Site 1303)
state: Isere
city: Nantes
country: France
facility: CHU de Nantes - Hoptal Nord Laennec ( Site 1309)
state: Loire-Atlantique
city: Angers
country: France
facility: CHU Angers ( Site 1313)
state: Maine-et-Loire
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU de Nancy Hopitaux de Brabois ( Site 1308)
state: Meurthe-et-Moselle
city: Lille
country: France
facility: CHRU Lille ( Site 1306)
state: Nord
city: Rouen
country: France
facility: CHU de Rouen ( Site 1323)
state: Seine-Maritime
city: Le Kremlin Bicêtre
country: France
facility: Centre Hospitalier Universitaire de Bicetre ( Site 1304)
state: Val-de-Marne
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH ( Site 1509)
state: Baden-Wurttemberg
city: München
country: Germany
facility: Krankenhaus Neuwittelsbach ( Site 1510)
state: Bayern
city: Regensburg
country: Germany
facility: University Hospital Regensburg ( Site 1503)
state: Bayern
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik-Forschungs-GmbH ( Site 1514)
state: Hessen
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH ( Site 1512)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 1505)
state: Niedersachsen
city: Cologne
country: Germany
facility: Uniklinik Köln ( Site 1511)
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitaetsmedizin Johannes Gutenberg Universitaet Mainz ( Site 1515)
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden. ( Site 1501)
state: Sachsen
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend ( Site 1507)
city: Ashdod
country: Israel
facility: Assuta Ashdod Medical Center ( Site 1710)
city: Be'er Ya'akov
country: Israel
facility: Shamir Medical Center Assaf Harofeh ( Site 1713)
city: Haifa
country: Israel
facility: Rambam Health Corp. ( Site 1716)
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center ( Site 1705)
city: Holon
country: Israel
facility: Edith Wolfson Medical Center ( Site 1717)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 1715)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 1711)
city: Kfar Saba
country: Israel
facility: Meir Medical Center. ( Site 1707)
city: Petah Tiqwa
country: Israel
facility: Rabin Medical Center ( Site 1703)
city: Rehovot
country: Israel
facility: Kaplan Medical Center ( Site 1712)
city: Safed
country: Israel
facility: ZIV Medical Center ( Site 1704)
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center ( Site 1714)
city: Bologna
country: Italy
facility: AOU di Bologna Policlinico S Orsola Malpighi ( Site 2409)
state: Emilia-Romagna
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)
state: Friuli-Venezia Giulia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza - A. O. San Gerardo ( Site 2406)
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS-Policlinico San Matteo ( Site 2401)
state: Lombardia
city: Sassari
country: Italy
facility: Ospedale SS Annunziata ( Site 2408)
state: Sardegna
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII ( Site 2410)
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I ( Site 2402)
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica En Medicina SC ( Site 2505)
state: Nuevo Leon
city: Lodz
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im dr WI Bieganskiego w Lodzi ( Site 2807)
state: Lodzkie
city: Lubin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego ( Site 2806)
state: Lubelskie
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2801)
state: Malopolskie
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Państwowy Instytut Medyczny MSWiA ( Site 2805)
state: Mazowieckie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku - Marii Sklodowskiej-Curie 24A ( Site 2803)
state: Podlaskie
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie ( Site 2804)
state: Zachodniopomorskie
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)
state: Madrid
city: Marbella
country: Spain
facility: Hospital Costa del Sol ( Site 1613)
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona ( Site 1602)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 1603)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena ( Site 1612)
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo ( Site 1607)
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 3201)
state: Vastra Gotalands Lan
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust ( Site 1203)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: