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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04576988
Recruitment Status : Completed
First Posted : October 6, 2020
Results First Posted : August 23, 2023
Last Update Posted : March 28, 2024
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Biological: Sotatercept
Drug: Placebo
Drug: Background PAH Therapy
Enrollment 324
Recruitment Details 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.
Pre-assignment Details Per protocol, not all participants from the double-blind placebo controlled (DBPC) period entered the long-term double blind (LTDB) period due to clinical worsening or consent withdrawal after DBPC period.
Arm/Group Title Sotatercept Plus Background PAH Therapy Placebo Plus Background PAH Therapy
Hide Arm/Group Description Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the double-blind placebo controlled (DBPC) period for up to approximately 24 weeks. After 24 weeks, participants received sotatercept dose titrated up to 0.7mg/kg SC injection every 21 days plus background PAH therapy during the long-term double blind (LTDB) period for up to approximately 72 weeks. Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks and the LTDB period for up to approximately 72 weeks.
Period Title: Double Blind Placebo Controlled (DBPC)
Started 163 160
Treated 163 160
Completed 159 148
Not Completed 4 12
Reason Not Completed
Adverse Event             1             1
Withdrawal by Subject             2             3
Protocol Violation             1             1
Death             0             5
Clinical worsening event             0             2
Period Title: Long Term Double Blind (LTDB)
Started 159 142 [1]
Treated 158 142
Completed 155 136
Not Completed 4 6
Reason Not Completed
Adverse Event             2             0
Withdrawal by Subject             0             3
Protocol Violation             0             1
Death             2             1
Sponsor decision             0             1
[1]
Not all participants from placebo plus background PAH arm in the DBPC period entered the LTDB period due to clinical worsening or consent withdrawal after DBPC period.
Arm/Group Title Sotatercept Plus Background PAH Therapy Placebo Plus Background PAH Therapy Total
Hide Arm/Group Description Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the double-blind placebo controlled (DBPC) period for up to approximately 24 weeks. After 24 weeks, participants received sotatercept dose titrated up to 0.7mg/kg SC injection every 21 days plus background PAH therapy during the long-term double blind (LTDB) period for up to approximately 72 weeks. Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks and the LTDB period for up to approximately 72 weeks. Total of all reporting groups
Overall Number of Baseline Participants 163 160 323
Hide Baseline Analysis Population Description
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  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 163 participants 160 participants 323 participants
47.6  (14.09) 48.3  (15.50) 47.9  (14.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 323 participants
Female
129
  79.1%
127
  79.4%
256
  79.3%
Male
34
  20.9%
33
  20.6%
67
  20.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 323 participants
Hispanic or Latino
27
  16.6%
31
  19.4%
58
  18.0%
Not Hispanic or Latino
132
  81.0%
124
  77.5%
256
  79.3%
Unknown or Not Reported
4
   2.5%
5
   3.1%
9
   2.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 323 participants
American Indian or Alaska Native
0
   0.0%
1
   0.6%
1
   0.3%
Asian
1
   0.6%
6
   3.8%
7
   2.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.6%
1
   0.3%
Black or African American
2
   1.2%
5
   3.1%
7
   2.2%
White
147
  90.2%
141
  88.1%
288
  89.2%
More than one race
7
   4.3%
4
   2.5%
11
   3.4%
Unknown or Not Reported
6
   3.7%
2
   1.3%
8
   2.5%
6-Minute Walk Distance (6MWD) at baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 163 participants 160 participants 323 participants
397.6  (84.28) 404.7  (80.59) 401.1  (82.4)
[1]
Measure Description: The 6MWD is the distance walked in 6 minutes as a measure of functional capacity.
World Health Organization (WHO) functional class (FC) II or III at baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 323 participants
Class II
79
  48.5%
78
  48.8%
157
  48.6%
Class III
84
  51.5%
82
  51.2%
166
  51.4%
[1]
Measure Description:

WHO FC was used to rate how ill a pulmonary arterial hypertension (PAH) participant was.

Class II: Participants with PAH resulting in a slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.

Class III: Participants with PAH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope
Background PAH Therapy at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 323 participants
Monotherapy
9
   5.5%
4
   2.5%
13
   4.0%
Double therapy
56
  34.4%
56
  35.0%
112
  34.7%
Triple therapy
98
  60.1%
100
  62.5%
198
  61.3%
[1]
Measure Description: Background PAH therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy (double or triple therapy) with endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists.
1.Primary Outcome
Title Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and had a baseline value of 6MWD.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: meters
34.4
(32.5 to 35.5)
1.0
(-1.0 to 5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method Aligned Rank Stratified Wilcoxon (ARSW)
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 40.8
Confidence Interval (2-Sided) 95%
27.53 to 54.14
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% confidence interval (CI) was reported.
2.Primary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Measure Type: Count of Participants
Unit of Measure: Participants
138
  84.7%
140
  87.5%
3.Primary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Measure Type: Count of Participants
Unit of Measure: Participants
3
   1.8%
10
   6.3%
4.Secondary Outcome
Title Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the multicomponent improvement.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 162 159
Measure Type: Number
Unit of Measure: Percent change
38.9 10.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments A 2-sided p-value was calculated using Cochran-Mantel-Haenszel (CMH) method with WHO FC II/III and background PAH therapy as strata.
5.Secondary Outcome
Title Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the PVR.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: dynes*sec/cm^5
-165.1
(-184.0 to -152.0)
32.8
(24.0 to 40.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method ARSW test
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -234.6
Confidence Interval (2-Sided) 95%
-288.37 to -180.75
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
6.Secondary Outcome
Title Change From Baseline in NT-proBNP Levels at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the NT-proBNP levels.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DPBC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: pg/mL
-230.3
(-236.0 to -223.0)
58.6
(44.0 to 73.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DPBC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method ARSW test
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -441.6
Confidence Interval (2-Sided) 95%
-573.54 to -309.61
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
7.Secondary Outcome
Title Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the WHO FC.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 159
Measure Type: Number
Unit of Measure: Percent change
29.4 13.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments A 2-sided p-value was calculated using CMH method with WHO FC II/III and background PAH therapy as strata.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Time to Death or the First Occurrence of Clinical Worsening Event
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who died or experienced a first clinical worsening event.
Arm/Group Title Sotatercept Plus Background PAH Therapy Placebo Plus Background PAH Therapy
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the double-blind placebo controlled (DBPC) period for up to approximately 24 weeks. After 24 weeks, participants received sotatercept dose titrated up to 0.7mg/kg SC injection every 21 days plus background PAH therapy during the long-term double blind (LTDB) period for up to approximately 72 weeks.
Participants received dose matched placebo by SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks and the LTDB period for up to approximately 72 weeks.
Overall Number of Participants Analyzed 163 160
Median (Standard Deviation)
Unit of Measure: Weeks
NA [1]   (NA) NA [1]   (NA)
[1]
NA = Median time and standard deviation (SD) could not be calculated due to insufficient number of participants who had the first occurrence of clinical worsening event or died.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy, Placebo Plus Background PAH Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments A 2-sided p-value was calculated using Log rank test with WHO FC II/III and background PAH therapy as strata.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.163
Confidence Interval (2-Sided) 95%
0.076 to 0.347
Estimation Comments Cox 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.
9.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the low risk score.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 162 159
Measure Type: Number
Unit of Measure: Percent Change
39.5 18.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments A 2-sided p-value was calculated using Cochran-Mantel-Haenszel (CMH) method with WHO FC II/III and background PAH therapy as strata.
10.Secondary Outcome
Title Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline physical impact domain score.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: Score on a scale
-0.13
(-0.15 to 0.00)
0.01
(0.00 to 0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method ARSW test
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.490 to -0.040
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
11.Secondary Outcome
Title Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline cardiopulmonary domain score.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: Score on a scale
-0.12
(-0.14 to -0.06)
-0.01
(-0.03 to 0.02)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method ARSW test
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.256 to -0.014
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
12.Secondary Outcome
Title Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and who had a baseline cognitive/emotional impacts domain score.
Arm/Group Title Sotatercept Plus Background PAH Therapy (DBPC Period) Placebo Plus Background PAH Therapy (DBPC Period)
Hide Arm/Group Description:
Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks.
Overall Number of Participants Analyzed 163 160
Median (Full Range)
Unit of Measure: Score on a scale
0.00
(0.00 to 0.00)
0.000007
(0.00 to 0.0006)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sotatercept Plus Background PAH Therapy (DBPC Period), Placebo Plus Background PAH Therapy (DBPC Period)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.156
Comments A 2-sided p-value was calculated using ARSW test with WHO FC II/III and background PAH therapy as strata.
Method ARSW test
Comments Participants who died were assigned the worst rank and who had missing data due to non-fatal clinical worsening event were assigned next worst-rank.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.399 to 0.084
Estimation Comments Hodges-Lehmann location-shift estimate of the overall treatment difference with 95% CI was reported.
Time Frame Up to approximately 19 months
Adverse Event Reporting Description All-cause mortality was reported on all randomized participants. Serious and non-serious adverse events were reported on all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Sotatercept 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)
Hide Arm/Group Description Participants received a starting dose of sotatercept 0.3 mg/kg titrated up to 0.7mg/kg by subcutaneous (SC) injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks. Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the DBPC period for up to approximately 24 weeks. Participants received sotatercept dose titrated up to 0.7mg/kg SC injection every 21 days plus background PAH therapy during the LTDB period for up to approximately 72 weeks. Participants received dose matched placebo SC injection every 21 days plus background PAH therapy during the LTDB period for up to approximately 72 weeks.
All-Cause Mortality
Sotatercept 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)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/163 (0.00%)      6/160 (3.75%)      2/159 (1.26%)      1/142 (0.70%)    
Hide Serious Adverse Events
Sotatercept 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)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/163 (14.11%)      36/160 (22.50%)      26/158 (16.46%)      14/142 (9.86%)    
Blood and lymphatic system disorders         
Anaemia † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Neutropenia † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Thrombocytopenia † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Cardiac disorders         
Acute coronary syndrome † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Acute myocardial infarction † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Atrial fibrillation † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 1/142 (0.70%)  1
Atrial flutter † 1  2/163 (1.23%)  2 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Cardiac arrest † 1  0/163 (0.00%)  0 2/160 (1.25%)  2 0/158 (0.00%)  0 0/142 (0.00%)  0
Cardiac failure † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Cardiac failure acute † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Cardiogenic shock † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Palpitations † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Right ventricular failure † 1  0/163 (0.00%)  0 2/160 (1.25%)  3 0/158 (0.00%)  0 1/142 (0.70%)  1
Stress cardiomyopathy † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Supraventricular tachycardia † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Endocrine disorders         
Hyperthyroidism † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Gastrointestinal disorders         
Abdominal distension † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Abdominal pain † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Abdominal pain upper † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Diarrhoea † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 1/142 (0.70%)  1
Gastritis † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Gastroduodenal ulcer † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Gastrointestinal haemorrhage † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 2/158 (1.27%)  3 0/142 (0.00%)  0
Haemorrhoidal haemorrhage † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Inguinal hernia † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Large intestine polyp † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Nausea † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Pancreatitis † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Upper gastrointestinal haemorrhage † 1  1/163 (0.61%)  2 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
General disorders         
Chest discomfort † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Chest pain † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Complication associated with device † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Vascular device occlusion † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 2/158 (1.27%)  3 0/142 (0.00%)  0
Hepatobiliary disorders         
Cholangitis acute † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Cholecystitis † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Immune system disorders         
Drug hypersensitivity † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Sarcoidosis † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Infections and infestations         
Bronchitis † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
COVID-19 † 1  0/163 (0.00%)  0 2/160 (1.25%)  2 2/158 (1.27%)  2 0/142 (0.00%)  0
COVID-19 pneumonia † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 1/142 (0.70%)  1
Catheter site infection † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 2/158 (1.27%)  2 0/142 (0.00%)  0
Cellulitis † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Device related sepsis † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Gastroenteritis † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Gastroenteritis viral † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Oesophageal candidiasis † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Perineal abscess † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Pneumonia † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 2/158 (1.27%)  2 0/142 (0.00%)  0
Pneumonia influenzal † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Post-acute COVID-19 syndrome † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Respiratory tract infection † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Sepsis † 1  1/163 (0.61%)  1 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Sepsis syndrome † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Septic shock † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Upper respiratory tract infection † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Vascular device infection † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Injury, poisoning and procedural complications         
Fall † 1  2/163 (1.23%)  2 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Humerus fracture † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Joint injury † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Neck injury † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Investigations         
Hepatic enzyme increased † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 1/158 (0.63%)  1 0/142 (0.00%)  0
Myocardial necrosis marker increased † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Weight decreased † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Metabolism and nutrition disorders         
Fluid retention † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Hypervolaemia † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 2/142 (1.41%)  2
Hypovolaemia † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Malnutrition † 1  0/163 (0.00%)  0 1/160 (0.63%)  2 0/158 (0.00%)  0 0/142 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Haemarthrosis † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Osteoporotic fracture † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Pain in extremity † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 1/158 (0.63%)  1 0/142 (0.00%)  0
Sjogren's syndrome † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Bladder cancer † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Breast cancer † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Intraductal proliferative breast lesion † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Ovarian neoplasm † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Nervous system disorders         
Cerebral haematoma † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Dizziness † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 1/158 (0.63%)  1 0/142 (0.00%)  0
Haemorrhage intracranial † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Syncope † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 1/142 (0.70%)  1
Product Issues         
Device dislocation † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Device leakage † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Device malfunction † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Device occlusion † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Device physical property issue † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 1/158 (0.63%)  1 1/142 (0.70%)  1
Nephritis † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Renal impairment † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Dyspnoea † 1  1/163 (0.61%)  1 2/160 (1.25%)  2 0/158 (0.00%)  0 0/142 (0.00%)  0
Dyspnoea exertional † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Epistaxis † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Haemoptysis † 1  2/163 (1.23%)  2 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Hypoxia † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Interstitial lung disease † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Pulmonary arterial hypertension † 1  1/163 (0.61%)  1 2/160 (1.25%)  2 0/158 (0.00%)  0 2/142 (1.41%)  2
Pulmonary artery aneurysm † 1  1/163 (0.61%)  1 0/160 (0.00%)  0 0/158 (0.00%)  0 0/142 (0.00%)  0
Pulmonary embolism † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Pulmonary hypertension † 1  0/163 (0.00%)  0 2/160 (1.25%)  2 0/158 (0.00%)  0 1/142 (0.70%)  1
Respiratory failure † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 0/158 (0.00%)  0 1/142 (0.70%)  1
Skin and subcutaneous tissue disorders         
Urticaria † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Vascular disorders         
Embolism venous † 1  0/163 (0.00%)  0 0/160 (0.00%)  0 1/158 (0.63%)  1 0/142 (0.00%)  0
Hypotension † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
Venous thrombosis limb † 1  0/163 (0.00%)  0 1/160 (0.63%)  1 0/158 (0.00%)  0 0/142 (0.00%)  0
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sotatercept 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)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   111/163 (68.10%)      88/160 (55.00%)      82/158 (51.90%)      50/142 (35.21%)    
Blood and lymphatic system disorders         
Thrombocytopenia † 1  8/163 (4.91%)  9 3/160 (1.88%)  3 8/158 (5.06%)  9 0/142 (0.00%)  0
Gastrointestinal disorders         
Diarrhoea † 1  20/163 (12.27%)  21 12/160 (7.50%)  13 6/158 (3.80%)  7 3/142 (2.11%)  4
Nausea † 1  17/163 (10.43%)  25 17/160 (10.63%)  26 8/158 (5.06%)  11 3/142 (2.11%)  5
General disorders         
Fatigue † 1  17/163 (10.43%)  20 12/160 (7.50%)  12 10/158 (6.33%)  12 4/142 (2.82%)  4
Injection site pain † 1  11/163 (6.75%)  12 10/160 (6.25%)  12 0/158 (0.00%)  0 1/142 (0.70%)  1
Oedema peripheral † 1  8/163 (4.91%)  10 10/160 (6.25%)  10 6/158 (3.80%)  7 3/142 (2.11%)  3
Infections and infestations         
COVID-19 † 1  24/163 (14.72%)  25 19/160 (11.88%)  19 24/158 (15.19%)  24 21/142 (14.79%)  21
Nasopharyngitis † 1  7/163 (4.29%)  9 9/160 (5.63%)  10 4/158 (2.53%)  4 5/142 (3.52%)  5
Urinary tract infection † 1  5/163 (3.07%)  5 3/160 (1.88%)  4 8/158 (5.06%)  8 3/142 (2.11%)  3
Metabolism and nutrition disorders         
Hypokalaemia † 1  9/163 (5.52%)  9 5/160 (3.13%)  5 6/158 (3.80%)  7 1/142 (0.70%)  1
Iron deficiency † 1  2/163 (1.23%)  2 7/160 (4.38%)  7 9/158 (5.70%)  9 3/142 (2.11%)  3
Nervous system disorders         
Dizziness † 1  17/163 (10.43%)  20 3/160 (1.88%)  4 6/158 (3.80%)  6 7/142 (4.93%)  7
Headache † 1  33/163 (20.25%)  41 24/160 (15.00%)  30 9/158 (5.70%)  9 6/142 (4.23%)  7
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  3/163 (1.84%)  4 12/160 (7.50%)  15 2/158 (1.27%)  2 6/142 (4.23%)  7
Epistaxis † 1  20/163 (12.27%)  24 3/160 (1.88%)  3 25/158 (15.82%)  36 1/142 (0.70%)  5
Skin and subcutaneous tissue disorders         
Rash † 1  9/163 (5.52%)  10 4/160 (2.50%)  5 5/158 (3.16%)  6 2/142 (1.41%)  2
Telangiectasia † 1  17/163 (10.43%)  21 5/160 (3.13%)  5 12/158 (7.59%)  16 2/142 (1.41%)  4
Vascular disorders         
Flushing † 1  9/163 (5.52%)  10 3/160 (1.88%)  5 2/158 (1.27%)  2 2/142 (1.41%)  2
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications of Results:
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.
Layout table for additonal information
Responsible Party: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
ClinicalTrials.gov Identifier: NCT04576988    
Other Study ID Numbers: 7962-003
7962-003 ( Other Identifier: Merck )
2020-004142-11 ( EudraCT Number )
First Submitted: September 28, 2020
First Posted: October 6, 2020
Results First Submitted: July 18, 2023
Results First Posted: August 23, 2023
Last Update Posted: March 28, 2024