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CompletedNCT04576988Updated Sep 19, 2024Results posted

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

A Phase 3 interventional study of Sotatercept and Placebo in Pulmonary Arterial Hypertension, sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA. Completed at 120 sites in 21 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA (part of Merck & Co., Inc) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
324
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed 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.

02

Conditions studied

  • Pulmonary Arterial Hypertension

Keywords

  • Pulmonary Hypertension
03

In context

Pulmonary Arterial Hypertension

773 studies on the registry are indexed under Pulmonary Arterial Hypertension; 142 are open to participants now.

This study's enrollment of 324 is above the median of 38 across 517 interventional studies indexed under Pulmonary Arterial Hypertension.

Browse Pulmonary Arterial Hypertension studies →

Lead sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA is the lead sponsor of 26 studies on the registry; none are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.

First submitted before Acceleron Pharma, Inc. became part of Merck & Co., Inc.

Browse Acceleron Pharma, Inc. studies →All Merck & Co., Inc studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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

    • Background PAH therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy with ERA, PDE5 inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists. Background PAH therapy should be stable at least 90 days prior to screening and remain stable throughout the study
    • Stable diuretic therapy is defined as no addition of a new diuretic and no switching of a pre-existent oral diuretic to parenteral administration; however, dose adjustments (up or down) in pre-existent oral diuretics are acceptable
  • 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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
324 participants (actual)

Study arms

  • Experimental
    Sotatercept plus background PAH therapy

    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

    Biological: Sotatercept · Drug: Background PAH Therapy

  • Placebo comparator
    Placebo plus background PAH therapy

    Placebo administered (SC) every 21 days plus background PAH therapy

    Drug: Placebo · Drug: Background PAH Therapy

Interventions

  • BiologicalSotatercept

    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.

    Also known as: MK-7962, ACE-011

  • DrugPlacebo

    Placebo administered subcutaneously (SC) every 21 days plus background PAH therapy.

  • DrugBackground 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.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and Week 24

  2. 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.

    Time frame: Up to approximately 24 weeks

  3. 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.

    Time frame: Up to approximately 24 weeks

Secondary outcomes

  1. 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.

    Time frame: Baseline and Week 24

  2. 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.

    Time frame: Baseline and Week 24

  3. 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.

    Time frame: Baseline and Week 24

  4. 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.

    Time frame: Baseline and Week 24

  5. 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.

    Time frame: Up to approximately 18 months

  6. 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.

    Time frame: Baseline and Week 24

  7. 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.

    Time frame: Baseline and Week 24

  8. 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.

    Time frame: Baseline and Week 24

  9. 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.

    Time frame: Baseline and Week 24

07

Results

Posted Aug 23, 2023

Participant flow

Of the 324 randomized participants, 1 participant was randomized in error and did not receive study treatment and no data was collected. Hence, the results are presented on 323 participants.

Double Blind Placebo Controlled (DBPC)
Participant flow — Double Blind Placebo Controlled (DBPC)
MilestoneSotatercept Plus Background PAH TherapyPlacebo Plus Background PAH Therapy
Started163160
Treated163160
Completed159148
Not completed412
Withdrew: Adverse event11
Withdrew: Withdrawal by subject23
Withdrew: Protocol violation11
Withdrew: Death05
Withdrew: Clinical worsening event02
Long Term Double Blind (LTDB)
Participant flow — Long Term Double Blind (LTDB)
MilestoneSotatercept Plus Background PAH TherapyPlacebo Plus Background PAH Therapy
Started159142
Treated158142
Completed155136
Not completed46
Withdrew: Adverse event20
Withdrew: Withdrawal by subject03
Withdrew: Protocol violation01
Withdrew: Death21
Withdrew: Sponsor decision01

Outcome measures

PrimaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · meters
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24
metersSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 2434.4 (32.5 to 35.5)1.0 (-1.0 to 5.0)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · Aligned Rank Stratified Wilcoxon (ARSW) · p = <0.001 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: 40.8 · 95% CI 27.53 to 54.14Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% confidence interval (CI) was reported.
PrimaryNumber 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.

Time frame:
Up to approximately 24 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Number of Participants Who Experienced an Adverse Event (AE)138140
PrimaryNumber 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.

Time frame:
Up to approximately 24 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Study Treatment Due to an AE
ParticipantsSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Number of Participants Who Discontinued Study Treatment Due to an AE310
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Number · Percent change
Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24
Percent changeSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 2438.910.1
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · Cochran-Mantel-Haenszel · p = <0.001A 2-sided p-value was calculated using Cochran-Mantel-Haenszel (CMH) method with WHO FC II/III and background PAH therapy as strata.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · dynes*sec/cm^5
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
dynes*sec/cm^5Sotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24-165.1 (-184.0 to -152.0)32.8 (24.0 to 40.0)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · ARSW test · p = <0.001 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: -234.6 · 95% CI -288.37 to -180.75Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · pg/mL
Change From Baseline in NT-proBNP Levels at Week 24
pg/mLSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DPBC Period)
Change From Baseline in NT-proBNP Levels at Week 24-230.3 (-236.0 to -223.0)58.6 (44.0 to 73.0)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DPBC Period) · ARSW test · p = <.001 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: -441.6 · 95% CI -573.54 to -309.61Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Number · Percent change
Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24
Percent changeSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 2429.413.8
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · Cochran-Mantel-Haenszel · p = <0.001
SecondaryTime 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.

Time frame:
Up to approximately 18 months
Reported as:
Median · Weeks
Time to Death or the First Occurrence of Clinical Worsening Event
WeeksSotatercept Plus Background PAH TherapyPlacebo Plus Background PAH Therapy
Time to Death or the First Occurrence of Clinical Worsening EventNA ± NANA ± NA
Statistical analysis
  • Sotatercept Plus Background PAH Therapy vs Placebo Plus Background PAH Therapy · Log Rank · p = <0.001 · Hazard ratio (hr): 0.163 · 95% CI 0.076 to 0.347Cox proportional hazard model was used to generate hazard ratio (HR) and 95% CI was reported with treatment group as the covariate stratified by the WHO FC II/III and background PAH therapy.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Number · Percent Change
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
Percent ChangeSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in Percentage of Participants Who Maintain or Achieve a Low Risk Score Using the Simplified French Risk Score Calculator at Week 2439.518.2
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · Cochran-Mantel-Haenszel · p = <0.001A 2-sided p-value was calculated using Cochran-Mantel-Haenszel (CMH) method with WHO FC II/III and background PAH therapy as strata.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · Score on a scale
Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24
Score on a scaleSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24-0.13 (-0.15 to 0.00)0.01 (0.00 to 0.14)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · ARSW test · p = 0.010 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: -0.26 · 95% CI -0.490 to -0.040Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · Score on a scale
Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24
Score on a scaleSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24-0.12 (-0.14 to -0.06)-0.01 (-0.03 to 0.02)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · ARSW test · p = 0.028 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: -0.13 · 95% CI -0.256 to -0.014Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
SecondaryChange 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.

Time frame:
Baseline and Week 24
Reported as:
Median · Score on a scale
Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24
Score on a scaleSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)
Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 240.00 (0.00 to 0.00)0.000007 (0.00 to 0.0006)
Statistical analysis
  • Sotatercept Plus Background PAH Therapy (DBPC Period) vs Placebo Plus Background PAH Therapy (DBPC Period) · ARSW test · p = 0.156 (A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.) · Treatment difference: -0.16 · 95% CI -0.399 to 0.084Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.

Adverse events

Collected over Up to approximately 19 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sotatercept Plus Background PAH Therapy (DBPC Period)0/163 (0%)23/163 (14.1%)111/163 (68.1%)
Placebo Plus Background PAH Therapy (DBPC Period)6/160 (3.8%)36/160 (22.5%)88/160 (55%)
Sotatercept Plus Background PAH Therapy (LTDB Period)2/159 (1.3%)26/158 (16.5%)82/158 (51.9%)
Placebo Plus Background PAH Therapy (LTDB Period)1/142 (0.7%)14/142 (9.9%)50/142 (35.2%)
Most frequent serious events
Showing 10 of 103
Most frequent serious events
EventSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)Sotatercept Plus Background PAH Therapy (LTDB Period)Placebo Plus Background PAH Therapy (LTDB Period)
HypervolaemiaMetabolism and nutrition disorders0/1631/1600/1582/142
Pulmonary arterial hypertensionRespiratory, thoracic and mediastinal disorders1/1632/1600/1582/142
Gastrointestinal haemorrhageGastrointestinal disorders0/1630/1602/1580/142
Vascular device occlusionGeneral disorders0/1630/1602/1580/142
COVID-19Infections and infestations0/1632/1602/1580/142
Catheter site infectionInfections and infestations0/1630/1602/1580/142
PneumoniaInfections and infestations1/1630/1602/1580/142
Cardiac arrestCardiac disorders0/1632/1600/1580/142
Right ventricular failureCardiac disorders0/1632/1600/1581/142
DyspnoeaRespiratory, thoracic and mediastinal disorders1/1632/1600/1580/142
Most frequent other events
Showing 10 of 18
Most frequent other events
EventSotatercept Plus Background PAH Therapy (DBPC Period)Placebo Plus Background PAH Therapy (DBPC Period)Sotatercept Plus Background PAH Therapy (LTDB Period)Placebo Plus Background PAH Therapy (LTDB Period)
HeadacheNervous system disorders33/16324/1609/1586/142
EpistaxisRespiratory, thoracic and mediastinal disorders20/1633/16025/1581/142
COVID-19Infections and infestations24/16319/16024/15821/142
DiarrhoeaGastrointestinal disorders20/16312/1606/1583/142
NauseaGastrointestinal disorders17/16317/1608/1583/142
FatigueGeneral disorders17/16312/16010/1584/142
DizzinessNervous system disorders17/1633/1606/1587/142
TelangiectasiaSkin and subcutaneous tissue disorders17/1635/16012/1582/142
DyspnoeaRespiratory, thoracic and mediastinal disorders3/16312/1602/1586/142
Injection site painGeneral disorders11/16310/1600/1581/142

Baseline characteristics

Of the 324 participants randomized in the study, one participant was randomized in error in placebo plus background PAH therapy arm and no data was collected on this participant. Per protocol, this participant was excluded from the study analysis.

Age, Continuous
Age, Continuous(Years)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Mean47.6 ± 14.0948.3 ± 15.5047.9 ± 14.79
Sex: Female, Male
Sex: Female, Male(Participants)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Female129127256
Male343367
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Hispanic or Latino273158
Not Hispanic or Latino132124256
Unknown or Not Reported459
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
American Indian or Alaska Native011
Asian167
Native Hawaiian or Other Pacific Islander011
Black or African American257
White147141288
More than one race7411
Unknown or Not Reported628
6-Minute Walk Distance (6MWD) at baseline
6-Minute Walk Distance (6MWD) at baseline(meters)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Mean397.6 ± 84.28404.7 ± 80.59401.1 ± 82.4
World Health Organization (WHO) functional class (FC) II or III at baseline
World Health Organization (WHO) functional class (FC) II or III at baseline(Participants)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Class II7978157
Class III8482166
Background PAH Therapy at Baseline
Background PAH Therapy at Baseline(Participants)Sotatercept Plus Background PAH TherapyPlacebo Plus Background PAH TherapyTotal
Monotherapy9413
Double therapy5656112
Triple therapy98100198
08

Study locations

120 sites
  • Arizona Pulmonary Specialists (Site 1010)
    Phoenix, Arizona 85012, United States
  • Pulmonary Associates, PA (Site 1008)
    Phoenix, Arizona 85032, United States
  • University of Arizona (Site 1006)
    Tucson, Arizona 85724, United States
  • University of California San Diego Medical Center (Site 1002)
    San Diego, California 92037, United States
  • University of California - Davis Medical Center (Site 1064)
    Sherman Oaks, California 95817, United States
  • Stanford University Medical Center (Site 1024)
    Stanford, California 94305, United States
  • Harbor UCLA Medical Center (Site 1028)
    Torrance, California 90502, United States
  • University of Colorado Hospital (Site 1013)
    Aurora, Colorado 80045, United States
  • The George Washington University Medical Faculty Associates (Site 1025)
    Washington D.C., District of Columbia 20037, United States
  • Mayo Clinic Jacksonville (Site 1045)
    Jacksonville, Florida 32256, United States
  • University of South Florida (Site 1043)
    Tampa, Florida 33606, United States
  • The Emory Clinic (Site 1030)
    Atlanta, Georgia 30322, United States
  • Norton Pulmonary Specialists (Site 1066)
    Louisville, Kentucky 40202, United States
  • Tufts Medical Center - PPDS (Site 1012)
    Boston, Massachusetts 02111, United States
  • Brigham and Women's Hospital (Site 1014)
    Boston, Massachusetts 02115, United States
  • University of Michigan (Site 1011)
    Ann Arbor, Michigan 48109-5936, United States
  • University of Minnesota (Site 1062)
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic (Site 1023)
    Rochester, Minnesota 55905, United States
  • University of Kansas Medical Center (Site 1020)
    Kansas City, Missouri 66160-7232, United States
  • Washington University School of Medicine (Site 1022)
    St Louis, Missouri 63110, United States
  • Nebraska Medical Center (Site 1053)
    Omaha, Nebraska 68105, United States
  • Renown Institute for Heart & Vascular Health (Site 1055)
    Reno, Nevada 89502-1262, United States
  • New York Presbyterian Hospital (Site 1046)
    New York, New York 10032, United States
  • Duke University Medical Center (Site 1026)
    Durham, North Carolina 27710, United States
  • University of Cincinnati Medical Center (Site 1035)
    Cincinnati, Ohio 45219-2316, United States
  • The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital (Site 1001)
    Cincinnati, Ohio 45219, United States
  • University Hospitals Cleveland Medical Center (Site 1005)
    Cleveland, Ohio 44106, United States
  • The Ohio State University Wexner Medical Center (Site 1032)
    Columbus, Ohio 43210, United States
  • Oregon Health and Science University (Site 1054)
    Portland, Oregon 97232, United States
  • University of Pennsylvania (Site 1047)
    Philadelphia, Pennsylvania 19104, United States
  • UPMC Presbyterian. UPMC Presbyterian Hospital (Site 1059)
    Pittsburgh, Pennsylvania 15213, United States
  • Rhode Island Hospital (Site 1033)
    Providence, Rhode Island 02903, United States
  • Medical University of South Carolina - PPDS (Site 1003)
    Charleston, South Carolina 29425-8900, United States
  • Statcare Pulmonary Consultants - Knoxville (Site 1031)
    Knoxville, Tennessee 37919, United States
  • Vanderbilt University Medical Center (Site 1027)
    Nashville, Tennessee 37232, United States
  • CHI St. Luke's Health Baylor College of Medicine Medical Center (Site 1044)
    Houston, Texas 77030, United States
  • Houston Methodist Hospital (Site 1009)
    Houston, Texas 77030, United States
  • University of Utah - PPDS (Site 1049)
    Salt Lake City, Utah 84132, United States
  • University of Washington Medical Center - Montlake (Site 1067)
    Seattle, Washington 98195-0001, United States
  • Hospital Universitario Austral ( Site 1901)
    Pilar, Buenos Aires B1629ODT, Argentina
  • Instituto de Investigaciones Clinicas Quilmes ( Site 1903)
    Quilmes, Buenos Aires B1878GEG, Argentina
  • Centro Medico Dra De Salvo ( Site 1904)
    Buenos Aires, Buenos Aires F.D. C1426ABP, Argentina
  • Sanatorio Parque ( Site 1905)
    Rosario, Santa Fe Province 2000, Argentina
  • Hospital Provincial Dr. Jose M. Cullen ( Site 1902)
    Santa Fe, S2732XAA, Argentina
  • Royal Prince Alfred Hospital ( Site 1106)
    Camperdown, New South Wales 2050, Australia
  • Saint Vincents Hospital Sydney ( Site 1102)
    Darlinghurst, New South Wales 2010, Australia
  • John Hunter Hospital ( Site 1101)
    New Lambton, New South Wales 2305, Australia
  • Westmead Hospital ( Site 1105)
    Westmead, New South Wales 2145, Australia
  • Prince Charles Hospital ( Site 1104)
    Chermside, Queensland 4032, Australia
  • The Alfred Hospital ( Site 1110)
    Melbourne, Victoria 3004, Australia
  • Hopital Erasme ( Site 1402)
    Brussels, Bruxelles-Capitale, Region de 1070, Belgium
  • U.Z.-Gasthuisberg ( Site 1401)
    Leuven, Vlaams-Brabant 3000, Belgium
  • Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 1805)
    Porto Alegre, Rio Grande do Sul 90020-090, Brazil
  • Hospital Dia do Pulmao ( Site 1802)
    Blumenau, Santa Catarina 89030-101, Brazil
  • Instituto do Coracao - HC FMUSP ( Site 1803)
    São Paulo, 05403-000, Brazil
  • University Of Alberta Hospital ( Site 2101)
    Edmonton, Alberta T6G 2E1, Canada
  • University of Ottawa Heart Institute ( Site 2104)
    Ottawa, Ontario K1Y 4W7, Canada
  • Jewish General Hospital ( Site 2103)
    Montreal, Quebec H3T 1E2, Canada
  • Fakultni Nemocnice Olomouc ( Site 2203)
    Olomouc, Olomouc Region 779 00, Czechia
  • Institut Klinicke a Experimentalni Mediciny ( Site 2202)
    Prague, Praha 4 140 21, Czechia
  • Vseobecna fakultni nemocnice v Praze ( Site 2201_
    Prague, Praha, Hlavni Mesto 128 08, Czechia
  • Hopital Pasteur (Site 1311)
    Nice, Alpes-Maritimes 06002, France
  • Hopitaux Universitaires de Strasbourg ( Site 1307)
    Strasbourg, Bas-Rhin 67000, France
  • CHRU Brest - Hopital Cavale Blanche (Site 1314)
    Brest, Finistere 29609, France
  • Groupe Hospitalier Sud ( Site 1312)
    Pessac, Gironde 33604, France
  • CHU de Toulouse - Hopital Larrey ( Site 1315)
    Toulouse, Haute-Garonne 31059, France
  • Hopital Arnaud de Villeneuve ( Site 1301)
    Montpellier, Herault 34090, France
  • CHU de Grenoble - Hopital Michallon ( Site 1303)
    Grenoble, Isere 38043, France
  • CHU Nantes - Hopital Laennec (Site 1309)
    Nantes, Loire-Atlantique 44093, France
  • CHU Angers (Site 1313)
    Angers, Maine-et-Loire 49100, France
  • C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308)
    Vandœuvre-lès-Nancy, Meurthe-et-Moselle 54500, France
  • CHRU Lille ( Site 1306)
    Lille, Nord 59037, France
  • Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302)
    Saint-Priest-en-Jarez, Pays de la Loire Region 42055, France
  • Centre Hospitalier Universitaire de Bicetre ( Site 1304)
    Le Kremlin-Bicêtre, Val-de-Marne 94270, France
  • Thoraxklinik-Heidelberg gGmbH (Site 1509)
    Heidelberg, Baden-Wurttemberg 69126, Germany
  • Krankenhaus Neuwittelsbach (Site 1510)
    Munich, Bavaria 80639, Germany
  • Universitaetsklinik Regensburg (Site 1503)
    Regensburg, Bavaria 93053, Germany
  • Universitaetsklinikum Giessen und Marburg GmbH ( Site 1512)
    Giessen, Hesse 35392, Germany
  • Medizinische Hochschule Hannover (Site 1505)
    Hanover, Lower Saxony 30625, Germany
  • Uniklinik Köln, Institut für Kliniche Chemie ( Site 1511)
    Cologne, North Rhine-Westphalia 50937, Germany
  • Universitaetsklinikum Carl Gustav Carus der TU Dresden (Site 1501)
    Dresden, Saxony 01307, Germany
  • Universitätsklinikum Halle (Site 1502)
    Halle, Saxony-Anhalt 06120, Germany
  • DRK Kliniken Berlin Westend ( Site 1507)
    Berlin, 14050, Germany
  • Lady Davis Carmel Medical Center (Site 1705)
    Haifa, 34362, Israel
  • Meir Medical Center (Site 1707)
    Kfar Saba, 4428164, Israel
  • Rabin Medical Center (Site 1703)
    Petah Tikva, 4941492, Israel
  • Sheba Medical Center (Site 1701)
    Tel Litwinsky, 5265601, Israel
  • Universita "La Sapienza" Policlinico Umberto I (Site 2402)
    Roma, 00161, Italy
  • CIMAB SA de CV (Site 2502)
    Torreón, Coahuila 27000, Mexico
  • Unidad de Investigacion Clinica en Medicina, S.C. (Site 2505)
    Monterrey, Nuevo León 64718, Mexico
  • Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas (Site 2501)
    Huixquilucan, 52763, Mexico
  • Maastricht University Medical Center (Site 2603)
    Maastricht, Limburg 6229 HX, Netherlands
  • VU Medisch Centrum (Site 2601)
    Amsterdam, North Holland 1081 HV, Netherlands
  • University of Otago, Wellington (Site 2701)
    Christchurch, Canterbury 8011, New Zealand
  • Waikato District Health Board (Site 2702)
    Hamilton, Waikato Region 3204, New Zealand
  • Greenlane Clinical Centre (Site 2703)
    Auckland, 1051, New Zealand
  • Krakowski Szpital Specjalistyczny im. Jana Pawla II (Site 2801)
    Krakow, Lesser Poland Voivodeship 31-202, Poland
  • Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina (Site 2802)
    Otwock, Masovian Voivodeship 05-400, Poland
  • Uniwersytecki Szpital Kliniczny w Bialymstoku (Site 2803)
    Bialystok, Podlaskie Voivodeship 15-276, Poland
  • Clinical Center of Serbia (Site 2901)
    Belgrade, Beograd 11000, Serbia

Showing the first 100 of 120 sites across 21 countries.

09

References and documents

Publications

  • 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 Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6. PubMed 36877098 ↗
  • Dutta S, Shah R, Singhal S, Singh M, Dholariya S, Chawla S, Katoch C. A systematic review and meta-analysis of safety and efficacy parameters of sotatercept in the therapy of pulmonary arterial hypertension. Expert Opin Drug Saf. 2026 Jun 9:1-13. doi: 10.1080/14740338.2026.2685360. Online ahead of print. PubMed 42246435 ↗
  • Alsumali A, McLaughlin V, Chevure J, Klok R, Zhang W, Martinez EC, Pausch C, De Oliveira Pena J, van de Wetering G, Jootun M, Lautsch D, Hoeper MM. Long-Term Mortality and Morbidity Impact on Patients with Pulmonary Arterial Hypertension (PAH) If Access to Sotatercept Is Delayed: A Simulation Model. Adv Ther. 2025 Aug;42(8):3902-3921. doi: 10.1007/s12325-025-03241-4. Epub 2025 Jun 17. PubMed 40526255 ↗
  • McLaughlin V, Alsumali A, Liu R, Klok R, Martinez EC, Nourhussein I, Bernotas D, Chevure J, Pausch C, De Oliveira Pena J, Lautsch D, Hoeper MM. Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). Adv Ther. 2024 Jan;41(1):130-151. doi: 10.1007/s12325-023-02684-x. Epub 2023 Oct 18. PubMed 37851297 ↗
  • Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Lin J, Johnson-Levonas AO, de Oliveira Pena J, Humbert M, Hoeper MM. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J. 2023 Sep 21;62(3):2301107. doi: 10.1183/13993003.01107-2023. Print 2023 Sep. PubMed 37696565 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 6, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Data sharing details ↗ · engagezone.msd.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04576988
Lead sponsor
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Responsible party
Sponsor
First posted
Oct 6, 2020
Start date
Jan 25, 2021
Primary completion
Aug 26, 2022
Completion
Dec 6, 2022
Results posted
Aug 23, 2023
Last update
Sep 19, 2024

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Sotatercept

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