Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13)

Pulmonary Arterial Hypertension Clinical Trial

— HYPERION  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04811092
• Other study ID #: 7962-005
• Secondary ID: A011-13MK-7962-0
• Status: Recruiting
• Phase: Phase 3
• Start date: March 18, 2022
• Est. completion date: December 27, 2029

Study information

• Verified date: May 2024
• Source: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 444
• Est. completion date: December 27, 2029
• Est. primary completion date: August 27, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Sotatercept
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

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Cardiologia Palermo ( Site 1911)	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Centro Medico Dra De Salvo ( Site 1904)	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Sanatorio Allende ( Site 1908)	Cordoba
Argentina	Instituto Médico DAMIC ( Site 1909)	Córdoba	Cordoba
Argentina	Hospital Universitario Austral ( Site 1901)	Pilar	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes ( Site 1903)	Quilmes	Buenos Aires
Argentina	Instituto Medico Rio Cuarto ( Site 1907)	Rio Cuarto	Cordoba
Argentina	Hospital Provincial del Centenario ( Site 1912)	Rosario	Santa Fe
Argentina	Instituto Cardiovascular de Rosario ( Site 1906)	Rosario	Santa Fe
Argentina	Sanatorio Parque ( Site 1905)	Rosario	Santa Fe
Argentina	Hospital Provincial Dr. Jose M. Cullen ( Site 1902)	Santa Fe
Argentina	Instituto De Enfermedades Respiratorias E Investigacion Medica ( Site 1910)	Villa Vatteone	Buenos Aires
Australia	Royal Adelaide Hospital ( Site 1109)	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital ( Site 1106)	Camperdown	New South Wales
Australia	Prince Charles Hospital ( Site 1104)	Chermside	Queensland
Australia	Royal Hobart Hospital ( Site 1107)	Hobart	Tasmania
Australia	Fiona Stanley Hospital ( Site 1103)	Murdoch	Western Australia
Australia	John Hunter Hospital ( Site 1101)	Newcastle	New South Wales
Australia	Princess Alexandra Hospital ( Site 1108)	Woolloongabba	Queensland
Austria	Medizinische Universität Graz ( Site 2003)	Graz	Steiermark
Austria	Medizinische Universitat Innsbruck ( Site 2004)	Innsbruck	Tirol
Austria	Ordensklinikum Linz GmbH Elisabethinen ( Site 2002)	Linz	Oberosterreich
Austria	Medizinische Universitat Wien ( Site 2001)	Wien
Belgium	Hopital Erasme ( Site 1402)	Anderlecht	Bruxelles-Capitale, Region De
Belgium	UZ Gasthuisberg ( Site 1401)	Leuven	Vlaams-Brabant
Brazil	Hospital Madre Teresa ( Site 1804)	Belo Horizonte	Minas Gerais
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto do Coracao - HCFMUSP ( Site 1803)	Sao Paulo
Brazil	Hospital Sao Paulo ( Site 1806)	São Paulo	Sao Paulo
Canada	University of Alberta Hospital ( Site 2101)	Edmonton	Alberta
Canada	St. Joseph's Healthcare Hamilton ( Site 2105)	Hamilton	Ontario
Canada	Sir Mortimer B Davis Jewish General Hospital ( Site 2103)	Montreal	Quebec
Canada	St Boniface General Hospital ( Site 2106)	Winnepeg	Manitoba
Colombia	Fundacion Neumologica Colombiana ( Site 3403)	Bogota	Cundinamarca
Colombia	Centro Cardiovascular Colombiano Clínica Santa María Clínica Cardio VID ( Site 3402)	Medellin	Antioquia
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 3404)	Santiago de Cali	Valle Del Cauca
Colombia	Fundacion Valle Del Lili ( Site 3401)	Santiago De Cali	Valle Del Cauca
Croatia	University Hospital Centre Split city ( Site 3901)	Split	Splitsko-dalmatinska Zupanija
Croatia	Klinicki Bolnicki Centar Zagreb ( Site 3902)	Zagreb	Zagrebacka Zupanija
Czechia	Institut Klinicke a Experimentalni Mediciny ( Site 2202)	Prague	Praha 4
Czechia	Vseobecna fakultni nemocnice v Praze ( Site 2201)	Praha 2
Denmark	Aarhus Universitetshospital, Skejby ( Site 3801)	Aarhus	Midtjylland
Denmark	Rigshospitalet ( Site 3802)	København Ø	Hovedstaden
France	CHU Angers ( Site 1313)	Angers	Maine-et-Loire
France	Hopital Haut Leveque ( Site 1312)	Bordeaux	Gironde
France	Hopital Cavale Blanche ( Site 1314)	Brest	Bretagne
France	CHU Caen Normandie ( Site 1325)	Caen	Calvados
France	CHU de Grenoble - Hopital Michallon ( Site 1303)	Grenoble	Isere
France	CHU - Hopital de Bicetre ( Site 1304)	Le Kremlin Bicetre	Val-de-Marne
France	Hopital Louis Pradel ( Site 1317)	Lyon	Auvergne
France	Hopital Nord Laennec ( Site 1309)	Nantes	Loire-Atlantique
France	Hopital Louis Pasteur ( Site 1311)	Nice	Alpes-Maritimes
France	CHU de Poitiers ( Site 1316)	Poitiers	Vienne
France	Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)	Saint-Priest-en-Jarez	Loire
France	Hopitaux Universitaires de Strasbourg ( Site 1307)	Strasbourg	Bas-Rhin
France	CHU de Toulouse - Hopital Larrey ( Site 1315)	Toulouse	Haute-Garonne
France	C.H.U. de Tours - Hopital Bretonneau ( Site 1310)	Tours	Indre-et-Loire
France	C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)	Vandoeuvre Les Nancy	Meurthe-et-Moselle
Germany	Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)	Bad Oeynhausen	Nordrhein-Westfalen
Germany	DRK Kliniken Berlin Westend ( Site 1507)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 1501)	Dresden	Sachsen
Germany	Universitaetsklinik und Poliklinik Halle/Saale ( Site 1502)	Halle	Sachsen-Anhalt
Germany	Medizinische Hochschule Hannover ( Site 1505)	Hannover	Niedersachsen
Germany	Thoraxklinik-Heidelberg gGmbH ( Site 1509)	Heidelberg	Baden-Wurttemberg
Germany	Universitatsklinikum des Saarlandes ( Site 1513)	Homburg	Saarland
Germany	Uniklinik Köln ( Site 1511)	Koln	Nordrhein-Westfalen
Germany	Universitatsklinikum Leipzig ( Site 1508)	Leipzig	Sachsen
Germany	Krankenhaus Neuwittelsbach ( Site 1510)	Muenchen	Bayern
Germany	Universitaetsklinik Regensburg ( Site 1503)	Regensburg	Bayern
Greece	Onassis Cardiac Surgery Center ( Site 3602)	Athens	Attiki
Greece	Evangelismos General Hospital of Athens ( Site 3605)	Athina	Attiki
Greece	Attikon University General Hospital of Athens ( Site 3604)	Haidari	Attiki
Greece	AHEPA University General Hospital of Thessaloniki ( Site 3601)	Thessaloniki
Israel	Assuta Ashdod Medical Center ( Site 1710)	Ashdod
Israel	Lady Davis Carmel Medical Center ( Site 1705)	Haifa
Israel	Hadassah Medical Center ( Site 1711)	Jerusalem
Israel	Sheba Medical Center ( Site 1701)	Ramat Gan
Italy	Ospedale S. Giuseppe Multimedica ( Site 2403)	Milan	Lombardia
Italy	Azienda Ospedaliera San Gerardo di Monza ( Site 2406)	Monza	Monza E Brianza
Italy	Azienda Ospedaliera R. N. V. Monaldi ( Site 2407)	Napoli
Italy	Azienda Policlinico Umberto I ( Site 2402)	Roma
Italy	Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) ( Site 2405)	Trieste	Friuli-Venezia Giulia
Korea, Republic of	Chonnam National University Hospital ( Site 3105)	Gwangju	Kyonggi-do
Korea, Republic of	Gachon University Gil Medical Center ( Site 3103)	Namdong-Gu	Incheon
Korea, Republic of	Seoul National University Hospital ( Site 3102)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System - PPDS ( Site 3101)	Seoul
Korea, Republic of	The Catholic University of Korea St. Mary s Hospital ( Site 3104)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 3106)	Seuol	Seoul
Netherlands	VU Medisch Centrum ( Site 2601)	Amsterdam	Noord-Holland
Netherlands	Maastricht University Medical Center ( Site 2603)	Maastricht	Limburg
Netherlands	Radboud University Nijmegen Medical Centre ( Site 2605)	Nijmegen	Gelderland
Netherlands	Erasmus MC ( Site 2604)	Rotterdam	Zuid-Holland
New Zealand	Waikato District Health Board ( Site 2702)	Hamilton	Waikato
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 2801)	Krakow	Malopolskie
Poland	Europejskie Centrum Zdrowia Otwock Szpital im Fryderyka Chopina ( Site 2802)	Otwock	Mazowieckie
Portugal	Hospital Garcia de Orta ( Site 3501)	Almada	Setubal
Portugal	Centro Hospitalar E Universitário De Coimbra ( Site 3502)	Coimbra
Portugal	Hospital Pulido Valente ( Site 3503)	Lisboa
Serbia	Clinical Center of Serbia ( Site 2901)	Beograd
Serbia	Clinical Center Kragujevac ( Site 2905)	Kragujevac	Sumadijski Okrug
Serbia	University Clinical Center Nis ( Site 2904)	Nis	Nisavski Okrug
Serbia	Institute for pulmonary diseases of Vojvodina ( Site 2906)	Sremska kamenica	Juznobacki Okrug
Spain	Hospital Universitari Vall de Hebron ( Site 1605)	Barcelona
Spain	Hospital Universitario 12 de Octubre ( Site 1603)	Madrid
Spain	Hospital Universitario La Paz ( Site 1610)	Madrid
Spain	Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1604)	Majadahonda	Madrid
Spain	Hospital Universitario de Son Espases ( Site 1611)	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 1608)	Salamanca
Spain	Hospital Universitario Marques de Valdecilla ( Site 1601)	Santander	Cantabria
Spain	Hospital Universitario de Toledo ( Site 1607)	Toledo
Sweden	Skanes Universitetssjukhus Lund ( Site 3203)	Lund	Skane Lan
Sweden	Norrlands Universitetssjukhus ( Site 3205)	Umea	Vasterbottens Lan
Sweden	Akademiska Sjukhuset [Uppsala, Sweden] ( Site 3204)	Uppsala	Uppsala Lan
Switzerland	UniversitätsSpital Zürich ( Site 3301)	Zurich
Taiwan	Kaohsiung Veterans General Hospital ( Site 3702)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 3701)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 3703)	Tainan
United Kingdom	Papworth Hospital NHS Foundation Trust ( Site 1208)	Cambrigge	Cambridgeshire
United Kingdom	Golden Jubilee National Hospital ( Site 1204)	Glasgow	Glasgow City
United Kingdom	Imperial College Healthcare NHS Trust ( Site 1203)	London	London, City Of
United Kingdom	Royal Brompton Hospital ( Site 1206)	London	London, City Of
United Kingdom	Royal Free London NHS Foundation Trust ( Site 1202)	London	London, City Of
United Kingdom	Freeman Hospital ( Site 1205)	Newcastle Upon Tyne
United Kingdom	Sheffield Teaching Hospital NHS Foundation Trust ( Site 1207)	Sheffield	Derbyshire
United States	University of New Mexico, Health Sciences Center ( Site 1048)	Albuquerque	New Mexico
United States	University of Michigan ( Site 1011)	Ann Arbor	Michigan
United States	University of Colorado Hospital ( Site 1013)	Aurora	Colorado
United States	Johns Hopkins Hospital ( Site 1036)	Baltimore	Maryland
United States	Brigham & Women's Hospital ( Site 1014)	Boston	Massachusetts
United States	Tufts Medical Center ( Site 1012)	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill ( Site 1042)	Chapel Hill	North Carolina
United States	Medical University of South Carolina ( Site 1003)	Charleston	South Carolina
United States	The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital ( Site 1001)	Cincinnati	Ohio
United States	University of Cincinnati Health ( Site 1035)	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation Taussig Cancer Center ( Site 1065)	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center ( Site 1038)	Dallas	Texas
United States	University of Iowa Hospital and Clinics ( Site 1050)	Iowa City	Iowa
United States	University of Kansas Medical Center ( Site 1020)	Kansas City	Missouri
United States	University of California San Diego ( Site 1002)	La Jolla	California
United States	David Geffen School of Medicine at UCLA ( Site 1068)	Los Angeles	California
United States	Vanderbilt University Medical Center ( Site 1027)	Nashville	Tennessee
United States	NYU Langone Health ( Site 1052)	New York	New York
United States	Nazih Zuhdi Transplantation Institute ( Site 1084)	Oklahoma City	Oklahoma
United States	University of California Irvine ( Site 1086)	Orange	California
United States	AdventHealth Medical Group Advanced Lung Disease ( Site 1058)	Orlando	Florida
United States	Arizona Pulmonary Specialists ( Site 1010)	Phoenix	Arizona
United States	Oregon Health & Science University ( Site 1054)	Portland	Oregon
United States	Washington University School of Medicine ( Site 1022)	Saint Louis	Missouri
United States	University of Utah ( Site 1049)	Salt Lake City	Utah
United States	Jeffrey S.Sager MD Medical Corporation ( Site 1060)	Santa Barbara	California
United States	University of California Davis Medical Center ( Site 1064)	Sherman Oaks	California
United States	University of Arizona ( Site 1006)	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Croatia,  Czechia,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Portugal,  Serbia,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Clinical Worsening	Time to clinical worsening is defined as time from randomization to the first confirmed morbidity event or death. Clinical worsening events are defined as all-cause death, non-planned PAH-related hospitalization of = 24 hours in duration, atrial septostomy, lung transplant and deterioration in performance in 6-minute walk test from baseline combined with one of the following conditions: worsening of WHO functional class from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral. All events will be adjudicated by a blinded, independent committee of clinical experts.	From time of randomization to the time of first clinical worsening event (Up to approximately 47 months)
Secondary	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)	Multicomponent improvement endpoint measured by the percentage of participants achieving all of the following at Week 24 relative to baseline: Improvement in 6MWD; Improvement or maintenance/achievement of NT-proBNP; Improvement in WHO FC or maintenance of WHO FC II	Baseline and Week 24
Secondary	Percentage of Participants who Achieved a Low Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 Risk Score	The REVEAL Lite 2 uses renal insufficiency (by estimated glomerular filtration rate (eGFR)), WHO FC, systolic blood pressure (SBP) and heart rate, 6MWD, and NT-proBNP to determine the total risk score. The scores (range: 1-14) can be defined as: low risk as a score of =5, intermediate risk as a score of 6 or 7, and high risk as a score of =8 for the survival rates.	Baseline and Week 24
Secondary	Percentage of Participants who Maintain or Achieve a Low Simplified French Risk Score	The simplified French Risk Score uses WHO FC, 6MWD, and NT-proBNP to determine the total risk score. A low risk score can be defined as attaining or maintaining all three low-risk criteria: WHO FC I or II, 6MWD > 440m, and NT-proBNP < 300 ng/L. The percentage of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French Risk score calculator will be reported.	Baseline and Week 24
Secondary	Change from Baseline in NT-proBNP Levels	Blood samples will be collected at baseline and at Week 24 to measure NT-proBNP blood concentration.	Baseline and Week 24
Secondary	Percentage of Participants who Improve in WHO FC or Maintain WHO FC II at 24 Weeks from Baseline	The severity of an individual's PAH symptoms was graded using the WHO FC system. WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO FC is classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC.	Baseline and Week 24
Secondary	Change from Baseline in 6MWD	The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity. Change from baseline in 6MWD at Week 24 will be reported.	Baseline and Week 24
Secondary	Change from Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT)®	PAH SYMPACT is a self-rating questionnaire to assess symptoms and their physical and cognitive/emotional impact. The PAH-SYMPACT® questionnaire consists of consists of 16 symptom and 25 impact items. A higher score indicates worse symptoms. Change from baseline in responses in PAH-SYMPACT questionnaire at Week 24 will be reported.	Baseline and Week 24
Secondary	Change from Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®	PAH SYMPACT is a self-rating questionnaire to assess symptoms and their physical and cognitive/emotional impact. The PAH-SYMPACT® questionnaire consists of consists of 16 symptom and 25 impact items. A higher score indicates worse symptoms. Change from baseline in responses in PAH-SYMPACT questionnaire at Week 24 will be reported.	Baseline and Week 24
Secondary	Change from Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT®	PAH SYMPACT is a self-rating questionnaire to assess symptoms and their physical and cognitive/emotional impact. The PAH-SYMPACT® questionnaire consists of consists of 16 symptom and 25 impact items. A higher score indicates worse symptoms. Change from baseline in responses in PAH-SYMPACT questionnaire at Week 24 will be reported	Baseline and Week 24

External Links

•   Merck Clinical Trials Information