A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR)

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare the Efficacy and Safety of Sotatercept Versus Placebo When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04576988
• Other study ID #: 7962-003
• Secondary ID: 7962-0032020-004
• Status: Completed
• Phase: Phase 3
• Start date: January 25, 2021
• Est. completion date: December 6, 2022

Study information

• Verified date: May 2024
• Source: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to evaluate the efficacy and safety of sotatercept (MK-7962) treatment (plus background pulmonary arterial hypertension (PAH) therapy) versus placebo (plus background PAH therapy) at 24 weeks in adults with PAH. The primary hypothesis of the study is that the participants receiving sotatercept will have improved 6-minute walk distance (6MWD) at 24 weeks compared to participants receiving placebo.

Description:

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study in subjects with symptomatic PAH who present with idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug or toxin induced, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects (CHDs), and currently on background PAH therapy. The primary efficacy endpoint of the study is exercise capacity, as measured by the 6-minute walk distance (6MWD) measured at 24 week following initiation of treatment. Study duration will be approximately 2 years. A stratified Wilcoxon test will be used for analysis of the primary endpoint, with appropriate imputation for missing data, as detailed in the Statistical Analysis Plan. An unblinded, external, independent Data Monitoring Committee (DMC) will monitor participant safety throughout the course of the study. Participants completing this study will be eligible to receive sotatercept in a separate, open-label extension study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: December 6, 2022
• Est. primary completion date: August 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Age = 18 years
• Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of World Health Organization (WHO) pulmonary arterial

hypertension (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
• Symptomatic PAH classified as WHO Functional Class (FC) II or III
• Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of = 5 Wood units (WU) and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure of = 15 mmHg.
• On stable doses of background PAH therapy and diuretics (i.e., patient-specific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice.
• 6-Minute Walk Distance (6MWD) = 150 and = 500 m repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value)
• Females of childbearing potential must:
• Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; she must agree to ongoing urine or serum pregnancy testing during the study and until 8 weeks after the last dose of the study drug
• If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, 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
• Male participants must:
• 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
• Ability to adhere to study visit schedule and understand and comply with all protocol requirements
• Ability to understand and provide written informed consent

Key Exclusion Criteria:

• Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
• Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension. Exclusions in PAH Group I should also include schistosomiasis associate PAH and pulmonary veno occlusive disease
• Hemoglobin (Hgb) at screening above gender-specific upper limit of normal (ULN), per local laboratory test
• Baseline platelet count < 50,000/mm^3 (< 50.0 x 109/L) at screening
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 100 mmHg during screening visit after a period of rest
• Baseline systolic blood pressure < 90 mmHg at screening
• Pregnant or breastfeeding women
• Any of the following clinical laboratory values at the screening visit:
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/m2 (as defined by the Modification of Diet in Renal Disease [MDRD] equation)
• Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels > 3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome)
• Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
• Prior exposure to sotatercept (ACE-011) or luspatercept (ACE 536) and/or excipients or known allergic reaction to either one
• History of full pneumonectomy
• Pulmonary function test (PFT) values of forced vital capacity (FVC) < 60% predicted at the screening visit or within 6 months prior to the screening visit. If PFT is not available, a chest CT scan showing more than mild interstitial lung disease (ILD) at the screening visit or 1 year prior to it
• 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)
• History of more than mild obstructive sleep apnea that is untreated
• Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A-C)
• History of restrictive, constrictive or congestive cardiomyopathy
• History of atrial septostomy within 180 days prior to the screening visit
• Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 500 ms during the screening period
• Personal or family history of long QT syndrome (LQTS) or sudden cardiac death
• Left ventricular ejection fraction < 45% on historical echocardiogram within 6 months prior to the screening visit
• Any symptomatic coronary disease events (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months prior to the screening visit. Note: Anginal pain can be ignored as an exclusion criterion if coronary angiography shows no obstructions
• Cerebrovascular accident within 3 months prior to the screening visit
• Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment
• Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Biological:
• Sotatercept
Sotatercept at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg administered subcutaneously (SC) every 21 days plus background PAH therapy.

Drug:
• Placebo
Placebo administered subcutaneously (SC) every 21 days plus background PAH therapy.
• Background PAH Therapy
Background PAH therapy may consist of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist.

Locations

Country	Name	City	State
Argentina	Centro Medico Dra De Salvo ( Site 1904)	Ciudad Autonoma de Buenos Aires	Caba
Argentina	Hospital Universitario Austral ( Site 1901)	Pilar	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes ( Site 1903)	Quilmes	Buenos Aires
Argentina	Sanatorio Parque ( Site 1905)	Rosario	Santa Fe
Argentina	Hospital Provincial Dr. Jose M. Cullen ( Site 1902)	Santa Fe
Australia	Royal Prince Alfred Hospital ( Site 1106)	Camperdown	New South Wales
Australia	Prince Charles Hospital ( Site 1104)	Chermside	Queensland
Australia	Saint Vincents Hospital Sydney ( Site 1102)	Darlinghurst	New South Wales
Australia	The Alfred Hospital ( Site 1110)	Melbourne	Victoria
Australia	John Hunter Hospital ( Site 1101)	New Lambton	New South Wales
Australia	Westmead Hospital ( Site 1105)	Westmead	New South Wales
Belgium	Hopital Erasme ( Site 1402)	Brussels	Bruxelles-Capitale, Region De
Belgium	U.Z.-Gasthuisberg ( Site 1401)	Leuven	Vlaams-Brabant
Brazil	Hospital Dia do Pulmao ( Site 1802)	Blumenau	Santa Catarina
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto do Coracao - HC FMUSP ( Site 1803)	Sao Paulo
Canada	University Of Alberta Hospital ( Site 2101)	Edmonton	Alberta
Canada	Jewish General Hospital ( Site 2103)	Montreal	Quebec
Canada	University of Ottawa Heart Institute ( Site 2104)	Ottawa	Ontario
Czechia	Fakultni Nemocnice Olomouc ( Site 2203)	Olomouc	Olomoucky Kraj
Czechia	Institut Klinicke a Experimentalni Mediciny ( Site 2202)	Prague	Praha 4
Czechia	Vseobecna fakultni nemocnice v Praze ( Site 2201_	Praha	Praha, Hlavni Mesto
France	CHU Angers (Site 1313)	Angers	Maine-et-Loire
France	CHRU Brest - Hopital Cavale Blanche (Site 1314)	Brest	Finistere
France	CHU de Grenoble - Hopital Michallon ( Site 1303)	Grenoble	Isere
France	Centre Hospitalier Universitaire de Bicetre ( Site 1304)	Le Kremlin Bicetre	Val-de-Marne
France	CHRU Lille ( Site 1306)	Lille	Nord
France	Hopital Arnaud de Villeneuve ( Site 1301)	Montpellier	Herault
France	CHU Nantes - Hopital Laennec (Site 1309)	Nantes	Loire-Atlantique
France	Hopital Pasteur (Site 1311)	Nice	Alpes-Maritimes
France	Groupe Hospitalier Sud ( Site 1312)	Pessac	Gironde
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 Nancy. Hopital de Brabois Adultes ( Site 1308)	Vandoeuvre Les Nancy	Meurthe-et-Moselle
Germany	DRK Kliniken Berlin Westend ( Site 1507)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus der TU Dresden (Site 1501)	Dresden	Sachsen
Germany	Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)	Giessen	Hessen
Germany	Universitätsklinikum Halle (Site 1502)	Halle (Saale)	Sachsen-Anhalt
Germany	Medizinische Hochschule Hannover (Site 1505)	Hannover	Niedersachsen
Germany	Thoraxklinik-Heidelberg gGmbH (Site 1509)	Heidelberg	Baden-Wurttemberg
Germany	Uniklinik Köln, Institut für Kliniche Chemie ( Site 1511)	Köln	Nordrhein-Westfalen
Germany	Krankenhaus Neuwittelsbach (Site 1510)	Muenchen	Bayern
Germany	Universitaetsklinik Regensburg (Site 1503)	Regensburg	Bayern
Israel	Lady Davis Carmel Medical Center (Site 1705)	Haifa
Israel	Meir Medical Center (Site 1707)	Kefar Saba
Israel	Rabin Medical Center (Site 1703)	Petah Tikva
Israel	Sheba Medical Center (Site 1701)	Tel Hashomer
Italy	Universita "La Sapienza" Policlinico Umberto I (Site 2402)	Roma
Korea, Republic of	Gachon University Gil Medical Center (Site 3103)	Incheon
Korea, Republic of	Seoul National University Hospital (Site 3102)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System - PPDS (Site 3101)	Seoul
Mexico	Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas (Site 2501)	Huixquilucan
Mexico	Unidad de Investigacion Clinica en Medicina, S.C. (Site 2505)	Monterrey	Nuevo Leon
Mexico	CIMAB SA de CV (Site 2502)	Torreon	Coahuila
Netherlands	VU Medisch Centrum (Site 2601)	Amsterdam	Noord-Holland
Netherlands	Maastricht University Medical Center (Site 2603)	Maastricht	Limburg
New Zealand	Greenlane Clinical Centre (Site 2703)	Auckland
New Zealand	University of Otago, Wellington (Site 2701)	Christchurch	Canterbury
New Zealand	Waikato District Health Board (Site 2702)	Hamilton	Waikato
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku (Site 2803)	Bialystok	Podlaskie
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
Serbia	Clinical Center of Serbia (Site 2901)	Belgrade	Beograd
Serbia	Institute of Cardiovascular Diseases Dedinje (Site 2903)	Belgrade	Beograd
Serbia	University Clinical Center Nis (Site 2904)	Nis	Nisavski Okrug
Spain	Hospital Clinic de Barcelona (Site 1602)	Barcelona
Spain	Hospital Universitari Vall d'Hebron (Site 1605)	Barcelona
Spain	Hospital Universitario Marques de Valdecilla (Site 1603)	Madrid
Spain	Hospital Universitario Ramon y Cajal (Site 1609)	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda (Site 1604)	Majadahonda	Madrid
Spain	Hospital Clinico Universitario de Salamanca (Site 1608)	Salamanca
Spain	Hospital Universitario Marques de Valdecilla (Site 1601)	Santander	Cantabria
Sweden	Sahlgrenska Universitets Sjukhuset (Site 3201)	Goteborg	Vastra Gotalands Lan
Sweden	Akademiska Sjukhuset (Site 3204)	Uppsala	Uppsala Lan
Switzerland	Hopitaux Universitaires de Geneve HUG (Site 3302)	Thonex	Geneve
Switzerland	Universitaetsspital Zuerich (Site 3301)	Zurich
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 States	University of Michigan (Site 1011)	Ann Arbor	Michigan
United States	The Emory Clinic (Site 1030)	Atlanta	Georgia
United States	University of Colorado Hospital (Site 1013)	Aurora	Colorado
United States	Brigham and Women's Hospital (Site 1014)	Boston	Massachusetts
United States	Tufts Medical Center - PPDS (Site 1012)	Boston	Massachusetts
United States	Medical University of South Carolina - PPDS (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 Medical Center (Site 1035)	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center (Site 1005)	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center (Site 1032)	Columbus	Ohio
United States	Duke University Medical Center (Site 1026)	Durham	North Carolina
United States	CHI St. Luke's Health Baylor College of Medicine Medical Center (Site 1044)	Houston	Texas
United States	Houston Methodist Hospital (Site 1009)	Houston	Texas
United States	Mayo Clinic Jacksonville (Site 1045)	Jacksonville	Florida
United States	University of Kansas Medical Center (Site 1020)	Kansas City	Missouri
United States	Statcare Pulmonary Consultants - Knoxville (Site 1031)	Knoxville	Tennessee
United States	Norton Pulmonary Specialists (Site 1066)	Louisville	Kentucky
United States	University of Minnesota (Site 1062)	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center (Site 1027)	Nashville	Tennessee
United States	New York Presbyterian Hospital (Site 1046)	New York	New York
United States	Nebraska Medical Center (Site 1053)	Omaha	Nebraska
United States	University of Pennsylvania (Site 1047)	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists (Site 1010)	Phoenix	Arizona
United States	Pulmonary Associates, PA (Site 1008)	Phoenix	Arizona
United States	UPMC Presbyterian. UPMC Presbyterian Hospital (Site 1059)	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University (Site 1054)	Portland	Oregon
United States	Rhode Island Hospital (Site 1033)	Providence	Rhode Island
United States	Renown Institute for Heart & Vascular Health (Site 1055)	Reno	Nevada
United States	Mayo Clinic (Site 1023)	Rochester	Minnesota
United States	Washington University School of Medicine (Site 1022)	Saint Louis	Missouri
United States	University of Utah - PPDS (Site 1049)	Salt Lake City	Utah
United States	University of California San Diego Medical Center (Site 1002)	San Diego	California
United States	University of Washington Medical Center - Montlake (Site 1067)	Seattle	Washington
United States	University of California - Davis Medical Center (Site 1064)	Sherman Oaks	California
United States	Stanford University Medical Center (Site 1024)	Stanford	California
United States	University of South Florida (Site 1043)	Tampa	Florida
United States	Harbor UCLA Medical Center (Site 1028)	Torrance	California
United States	University of Arizona (Site 1006)	Tucson	Arizona
United States	The George Washington University Medical Faculty Associates (Site 1025)	Washington	District of Columbia

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,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Serbia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Tri — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24	The 6MWD was the distance walked in 6 minutes as a measure of functional capacity. This was assessed using the 6-minute walk test (6MWT). Per protocol, change from baseline in 6MWD at Week 24 was reported for DBPC period.	Baseline and Week 24
Primary	Number of Participants Who Experienced an Adverse Event (AE)	An AE was any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. Per protocol, the number of participants who reported an AE were reported for DBPC period.	Up to approximately 24 weeks
Primary	Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for DBPC period.	Up to approximately 24 weeks
Secondary	Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24	Multicomponent Improvement was defined as consisting of all of the following: (a) Improvement in 6MWD (increase =30 meters) (b) Improvement in N-terminal pro b-type natriuretic peptide (NT-proBNP; decrease in NT-proBNP =30%) or maintenance/achievement of NT-proBNP level <300 ng/L (c) Improvement in World Health Organization (WHO) Functional Class (FC) or maintenance of WHO FC II. Per protocol, change from baseline in the percentage of participants achieving multicomponent improvement at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24	PVR is a hemodynamic variable of pulmonary circulation and was measured by right heart catheterization (RHC). Per protocol, the change from baseline in PVR at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in NT-proBNP Levels at Week 24	NT-proBNP is a circulating biomarker that reflects myocardial stretch. Per protocol, the change from baseline in NT-proBNP level at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24	The severity of participant's pulmonary arterial hypertension (PAH) symptoms will be graded using the WHO FC system. WHO functional classification for PAH ranges 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). Participants who improve in WHO FC were classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC. Per protocol, change from baseline in the percentage of participants who improve in WHO FC at Week 24 were reported for DBPC period.	Baseline and Week 24
Secondary	Time to Death or the First Occurrence of Clinical Worsening Event	Clinical Worsening events are defined as any of the following: worsening-related listing for lung and/or heart transplant; need to initiate rescue therapy with an approved background PAH therapy or the need to increase the dose of infusion prostacyclin by 10% or more; need for atrial septostomy; hospitalization for worsening of PAH (= 24 hours); or deterioration of PAH defined by both of the following events occurring at any time: worsened WHO FC and decrease in 6MWD by =15% confirmed by 2 tests at least 4 hours apart, but no more than 1 week. Per protocol, time to death or the first occurrence of clinical worsening event was reported.	Up to approximately 18 months
Secondary	Change From Baseline in Percentage of Participants Who Maintain or Achieve a Low Risk Score Using the Simplified French Risk Score Calculator at Week 24	The simplified French risk scoring system was based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension (PH). In this study, the noninvasive parameters were used to determine the score. 'Low risk' was defined as attaining or maintaining all 3 low-risk criteria: WHO FC I or II, 6MWD > 440 m, and NT-proBNP <300 ng/L. Per protocol, change from baseline in percentage of participants who maintained or achieved a low risk score using the simplified French risk score calculator at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure pulmonary arterial hypertension (PAH)-related symptoms and impact of PAH on daily life. The physical impact domain consists of walking slowly on a flat surface, walking quickly on a flat surface, walking uphill, carrying things, doing light indoor household chores, washing, or dressing oneself, and needing help from others. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no physical impact to 4=severe physical impact). A higher score indicated more severe physical impact. Per protocol, change from baseline in the physical impacts domain score at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The cardiopulmonary symptoms consist of shortness of breath, fatigue, lack of energy, swelling in the ankles or legs, swelling in the stomach area, and cough. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (no symptom at all) to 4 (very severe symptoms). The mean individual symptom item score was determined for each of the 6 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items (range: 0=no cardiopulmonary symptoms to 4=severe cardiopulmonary symptoms). A higher score indicated more severe symptoms experienced. Per protocol, change from baseline in the cardiopulmonary domain score at Week 24 was reported for DBPC period.	Baseline and Week 24
Secondary	Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24	The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The Cognitive/Emotional Impact domain consists of thinking clearly, feeling sad, feeling worried, and feeling frustrated. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no cognitive/emotional impact to 4=severe cognitive/emotional impact). A higher score indicated more severe cognitive/emotional impact. Per protocol, change from baseline in the cognitive/emotional impacts domain score at Week 24 was reported for DBPC period.	Baseline and Week 24

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary