Clinical trial NCT04811092: Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary
Hypertension
Sotatercept
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly called ACE-011) treatment (plus background pulmonary arterial hypertension (PAH) therapy) versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are at intermediate or high risk of disease progression.

Detailed description: This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to background PAH therapy in newly diagnosed intermediate- or high risk PAH participants.

Participants enrolled in the study will have a diagnosis within 12 months of study screening of symptomatic PAH (World Health Organization (WHO) Group 1, classified as functional class (FC) II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin- induced PAH, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects.

As of Amendment 11, this study will be closed so that all eligible participants can receive sotatercept either on the MK-7962-004 extension study (SOTERIA, NCT04796337,) or by commercial access, if available. All eligible participants will complete the end of treatment visit before enrollment in the extension study or initiation of commercial product. Participants not enrolling into the extension study or initiating commercial product will complete the end of study visit.

Eligibility criteria: Inclusion Criteria:

Eligible participants must meet all of the following criteria to be enrolled in the study:

1. Age ≥ 18 years
2. Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes:

   * Idiopathic PAH
   * Heritable PAH
   * Drug/toxin-induced PAH
   * PAH associated with connective tissue disease
   * PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
3. Symptomatic PAH classified as WHO FC II or III
4. Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or above)
5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening
6. Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)
7. Females of childbearing potential must meet the following criteria:

   * Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum 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, have used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed 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 treatment
8. Male participants must meet the following criteria:

   * Agree to use a condom, defined as a male latex condom or nonlatex 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 treatment
9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements
10. Ability to understand and provide written informed consent

Exclusion Criteria:

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

1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis
3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) \> 180 mmHg or sitting diastolic BP \> 110 mmHg during the Screening Visit after a period of rest
5. Baseline systolic BP \< 90 mmHg at screening
6. Pregnant or breastfeeding women
7. Any of the following clinical laboratory values at the Screening Visit:

   * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (as defined by MDRD equation)
   * Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels \> 3 × ULN
   * Platelet count \< 50,000/mm3 (\< 50.0 × 109 /L)
8. 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 informed consent
9. Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
10. History of pneumonectomy
11. Pulmonary function test values of forced vital capacity \< 60% predicted within 1 year prior to the Screening Visit
12. Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
13. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit 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)
14. Untreated more than mild obstructive sleep apnea
15. History of known pericardial constriction
16. History of restrictive or congestive cardiomyopathy
17. History of atrial septostomy within 180 days prior to the Screening Visit
18. Electrocardiogram with Fridericia's corrected QT interval \> 500 ms during the Screening Period
19. Personal or family history of long QT syndrome or sudden cardiac death
20. Left ventricular ejection fraction \< 50% on historical echocardiogram (ECHO) within 1 year prior to the Screening Visit
21. Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening Visit
22. Cerebrovascular accident within 3 months prior to the Screening Visit
23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
24. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit
26. Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment

Primary outcomes:
measure: Time to Clinical Worsening
timeFrame: Up to ~36 months
Secondary outcomes:
measure: Percentage of Participants Achieving the Multicomponent Improvement Endpoint of 6-Minute Walk Distance (6MWD), N-terminal prohormone Btype natriuretic peptide (NT-ProBNP) and World Health Organization (WHO) Functional Class (FC)
timeFrame: Baseline and Week 24
measure: Percentage of Participants who Achieved a Low Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 Risk Score
timeFrame: Baseline and Week 24
measure: Percentage of Participants who Maintain or Achieve a Low Simplified French Risk Score
timeFrame: Baseline and Week 24
measure: Change from Baseline in NT-proBNP Levels
timeFrame: Baseline and Week 24
measure: Percentage of Participants who Improve in WHO FC or Maintain WHO FC II at 24 Weeks from Baseline
timeFrame: Baseline and Week 24
measure: Change from Baseline in 6MWD
timeFrame: Baseline and Week 24
measure: Overall Survival (OS)
timeFrame: Up to ~36 Months
measure: Change from Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT)®
timeFrame: Baseline and Week 24
measure: Change from Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®
timeFrame: Baseline and Week 24
measure: Change from Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT®
timeFrame: Baseline and Week 24
measure: Number of Participants who Experience an Adverse Event (AE)
timeFrame: Up to ~36 Months
measure: Number of Participants who Discontinued Study Treatment due to AEs
timeFrame: Up to ~34 months
measure: Incidence of Anti-drug Antibodies (ADAs) to Sotatercept
timeFrame: Up to ~36 Months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Arizona Pulmonary Specialists ( Site 1010)
state: Arizona
city: Tucson
country: United States
facility: University of Arizona ( Site 1006)
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego ( Site 1002)
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center ( Site 1068)
state: California
city: Orange
country: United States
facility: University of California Irvine ( Site 1086)
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Pulmonary Associates ( Site 1060)
state: California
city: Sherman Oaks
country: United States
facility: University of California Davis Medical Center ( Site 1064)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital ( Site 1013)
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Medical Group Advanced Lung Disease ( Site 1058)
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics ( Site 1050)
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital ( Site 1036)
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center - PPDS ( Site 1014)
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center ( Site 1012)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 1011)
state: Michigan
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 1020)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine ( Site 1022)
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico, Health Sciences Center ( Site 1048)
state: New Mexico
city: New York
country: United States
facility: NYU Langone Health ( Site 1052)
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill ( Site 1042)
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: Cincinnati
country: United States
facility: University of Cincinnati ( Site 1035)
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation Taussig Cancer Center ( Site 1065)
state: Ohio
city: Oklahoma City
country: United States
facility: Nazih Zuhdi Transplantation Institute ( Site 1084)
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University ( Site 1054)
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina ( Site 1003)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 1027)
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center ( Site 1038)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah ( Site 1049)
state: Utah
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Cardiologia Palermo ( Site 1911)
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra De Salvo ( Site 1904)
state: Buenos Aires
city: Pilar
country: Argentina
facility: Hospital Universitario Austral ( Site 1901)
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes ( Site 1903)
state: Buenos Aires
city: Villa Vatteone
country: Argentina
facility: Instituto De Enfermedades Respiratorias E Investigacion Medica ( Site 1910)
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Instituto Médico DAMIC ( Site 1909)
state: Cordoba
city: Rio Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto ( Site 1907)
state: Cordoba
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario ( Site 1912)
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto Cardiovascular de Rosario ( Site 1906)
state: Santa Fe
city: Rosario
country: Argentina
facility: Sanatorio Parque ( Site 1905)
state: Santa Fe
city: Cordoba
country: Argentina
facility: Sanatorio Allende ( Site 1908)
city: Santa Fe
country: Argentina
facility: Hospital Provincial Dr. Jose M. Cullen ( Site 1902)
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital ( Site 1106)
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital ( Site 1101)
state: New South Wales
city: Chermside
country: Australia
facility: Prince Charles Hospital ( Site 1104)
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 1108)
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital ( Site 1109)
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital ( Site 1107)
state: Tasmania
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 1103)
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen ( Site 2002)
state: Oberosterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz ( Site 2003)
state: Steiermark
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck ( Site 2004)
state: Tirol
city: Vienna
country: Austria
facility: Medizinische Universitat Wien ( Site 2001)
state: Wien
city: Anderlecht
country: Belgium
facility: Hopital Erasme ( Site 1402)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Gasthuisberg ( Site 1401)
state: Vlaams-Brabant
city: Belo Horizonte
country: Brazil
facility: Hospital Madre Teresa ( Site 1804)
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Hospital Sao Paulo ( Site 1806)
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Coracao - HCFMUSP ( Site 1803)
city: Edmonton
country: Canada
facility: University of Alberta Hospital ( Site 2101)
state: Alberta
city: Winnepeg
country: Canada
facility: St Boniface General Hospital ( Site 2106)
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University - HSC ( Site 2105)
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B Davis Jewish General Hospital ( Site 2103)
state: Quebec
city: Medellin
country: Colombia
facility: Centro Cardiovascular Colombiano Clínica Santa María Clínica Cardio VID ( Site 3402)
state: Antioquia
city: Bogota
country: Colombia
facility: Fundacion Neumologica Colombiana ( Site 3403)
state: Cundinamarca
city: Santiago De Cali
country: Colombia
facility: Fundacion Valle Del Lili ( Site 3401)
state: Valle Del Cauca
city: Santiago de Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A ( Site 3404)
state: Valle Del Cauca
city: Split
country: Croatia
facility: University Hospital Centre Split city ( Site 3901)
state: Splitsko-dalmatinska Zupanija
city: Zagreb
country: Croatia
facility: Klinicki Bolnicki Centar Zagreb ( Site 3902)
state: Zagrebacka Zupanija
city: Prague
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny ( Site 2202)
state: Praha 4
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze ( Site 2201)
city: København Ø
country: Denmark
facility: Rigshospitalet ( Site 3802)
state: Hovedstaden
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby ( Site 3801)
state: Midtjylland
city: Nice
country: France
facility: Hopital Louis Pasteur ( Site 1311)
state: Alpes-Maritimes
city: Lyon
country: France
facility: Hopital Louis Pradel ( Site 1317)
state: Auvergne
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg ( Site 1307)
state: Bas-Rhin
city: Brest
country: France
facility: Hopital Cavale Blanche ( Site 1314)
state: Bretagne
city: Caen
country: France
facility: CHU Caen Normandie ( Site 1325)
state: Calvados
city: Besançon
country: France
facility: CHU de Besancon ( Site 1303)
state: Doubs
city: Bordeaux
country: France
facility: Hopital Haut Leveque ( Site 1312)
state: Gironde
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Larrey ( Site 1315)
state: Haute-Garonne
city: Tours
country: France
facility: C.H.U. de Tours - Hopital Bretonneau ( Site 1310)
state: Indre-et-Loire
city: Nantes
country: France
facility: Hopital Nord Laennec ( Site 1309)
state: Loire-Atlantique
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)
state: Loire
city: Angers
country: France
facility: CHU Angers ( Site 1313)
state: Maine-et-Loire
city: Vandoeuvre Les Nancy
country: France
facility: C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)
state: Meurthe-et-Moselle
city: Le Kremlin Bicetre
country: France
facility: CHU - Hopital de Bicetre ( Site 1304)
state: Val-de-Marne
city: Poitiers
country: France
facility: CHU de Poitiers ( Site 1316)
state: Vienne
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg ( Site 1509)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Krankenhaus Neuwittelsbach ( Site 1510)
state: Bayern
city: Regensburg
country: Germany
facility: Universitaetsklinik Regensburg ( Site 1503)
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 1505)
state: Niedersachsen
city: Bad Oeynhausen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)
state: Nordrhein-Westfalen
city: Koln
country: Germany
facility: Uniklinik Köln ( Site 1511)
state: Nordrhein-Westfalen
city: Homburg
country: Germany
facility: Universitatsklinikum des Saarlandes ( Site 1513)
state: Saarland
city: Halle
country: Germany
facility: Universitaetsklinik und Poliklinik Halle/Saale ( Site 1502)
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus ( Site 1501)
state: Sachsen
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig ( Site 1508)
state: Sachsen
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend ( Site 1507)
city: Athens
country: Greece
facility: Onassis Cardiac Surgery Center ( Site 3602)
state: Attiki
city: Athina
country: Greece
facility: Evangelismos General Hospital of Athens ( Site 3605)
state: Attiki
city: Haidari
country: Greece
facility: Attikon University General Hospital of Athens ( Site 3604)
state: Attiki
city: Thessaloniki
country: Greece
facility: AHEPA University General Hospital of Thessaloniki ( Site 3601)
city: Ashdod
country: Israel
facility: Assuta Ashdod Medical Center ( Site 1710)
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center ( Site 1705)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 1711)
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center ( Site 1701)
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)
state: Friuli-Venezia Giulia
city: Milan
country: Italy
facility: Ospedale S. Giuseppe Multimedica ( Site 2403)
state: Lombardia
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza ( Site 2406)
state: Monza E Brianza
city: Napoli
country: Italy
facility: Azienda Ospedaliera R. N. V. Monaldi ( Site 2407)
city: Roma
country: Italy
facility: La Sapienza-Università di Roma-Policlinico Umberto I ( Site 2402)
city: Namdong-Gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center ( Site 3103)
state: Incheon
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital ( Site 3105)
state: Kyonggi-do
city: Seuol
country: Korea, Republic of
facility: Samsung Medical Center ( Site 3106)
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 3102)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS ( Site 3101)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea St. Mary s Hospital ( Site 3104)
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre ( Site 2605)
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center ( Site 2603)
state: Limburg
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum ( Site 2601)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC ( Site 2604)
state: Zuid-Holland
city: Hamilton
country: New Zealand
facility: Waikato District Health Board ( Site 2702)
state: Waikato
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 2801)
state: Malopolskie
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc w Warszawie ( Site 2802)
state: Mazowieckie
city: Almada
country: Portugal
facility: Hospital Garcia de Orta ( Site 3501)
state: Setubal
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário De Coimbra ( Site 3502)
city: Lisboa
country: Portugal
facility: Hospital Pulido Valente ( Site 3503)
city: Sremska kamenica
country: Serbia
facility: Institute for pulmonary diseases of Vojvodina ( Site 2906)
state: Juznobacki Okrug
city: Nis
country: Serbia
facility: University Clinical Center Nis ( Site 2904)
state: Nisavski Okrug
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac ( Site 2905)
state: Sumadijski Okrug
city: Beograd
country: Serbia
facility: Clinical Center of Serbia ( Site 2901)
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla ( Site 1601)
state: Cantabria
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario de Son Espases ( Site 1611)
state: Islas Baleares
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall de Hebron ( Site 1605)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 1603)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 1610)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 1608)
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud ( Site 1607)
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Lund ( Site 3203)
state: Skane Lan
city: Uppsala
country: Sweden
facility: Hjart-lungmedicin och klinisk fysiologi ( Site 3204)
state: Uppsala Lan
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus ( Site 3205)
state: Vasterbottens Lan
city: Zurich
country: Switzerland
facility: UniversitätsSpital Zürich ( Site 3301)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital ( Site 3702)
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 3701)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 3703)
city: Cambrigge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust ( Site 1208)
state: Cambridgeshire
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital NHS Foundation Trust ( Site 1207)
state: Derbyshire
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital ( Site 1204)
state: Glasgow City
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust ( Site 1202)
state: London, City Of
city: London
country: United Kingdom
facility: Royal Brompton Hospital ( Site 1206)
state: London, City Of
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust ( Site 1203)
state: London, City Of
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital ( Site 1205)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: