Trial Outcomes & Findings for A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR) (NCT NCT04576988)

Last Updated: 2024-09-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

324 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2024-09-19

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.

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.

Participant milestones

Participant milestones
Measure	Sotatercept Plus Background PAH Therapy 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.	Placebo Plus Background PAH Therapy 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.
Double Blind Placebo Controlled (DBPC) STARTED	163	160
Double Blind Placebo Controlled (DBPC) Treated	163	160
Double Blind Placebo Controlled (DBPC) COMPLETED	159	148
Double Blind Placebo Controlled (DBPC) NOT COMPLETED	4	12
Long Term Double Blind (LTDB) STARTED	159	142
Long Term Double Blind (LTDB) Treated	158	142
Long Term Double Blind (LTDB) COMPLETED	155	136
Long Term Double Blind (LTDB) NOT COMPLETED	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Sotatercept Plus Background PAH Therapy 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.	Placebo Plus Background PAH Therapy 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.
Double Blind Placebo Controlled (DBPC) Adverse Event	1	1
Double Blind Placebo Controlled (DBPC) Withdrawal by Subject	2	3
Double Blind Placebo Controlled (DBPC) Protocol Violation	1	1
Double Blind Placebo Controlled (DBPC) Death	0	5
Double Blind Placebo Controlled (DBPC) Clinical worsening event	0	2
Long Term Double Blind (LTDB) Adverse Event	2	0
Long Term Double Blind (LTDB) Withdrawal by Subject	0	3
Long Term Double Blind (LTDB) Protocol Violation	0	1
Long Term Double Blind (LTDB) Death	2	1
Long Term Double Blind (LTDB) Sponsor decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sotatercept Plus Background PAH Therapy n=163 Participants 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.	Placebo Plus Background PAH Therapy n=160 Participants 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 n=323 Participants Total of all reporting groups
Age, Continuous	47.6 Years STANDARD_DEVIATION 14.09 • n=5 Participants	48.3 Years STANDARD_DEVIATION 15.50 • n=7 Participants	47.9 Years STANDARD_DEVIATION 14.79 • n=5 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	127 Participants n=7 Participants	256 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	31 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants n=5 Participants	124 Participants n=7 Participants	256 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	147 Participants n=5 Participants	141 Participants n=7 Participants	288 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
6-Minute Walk Distance (6MWD) at baseline	397.6 meters STANDARD_DEVIATION 84.28 • n=5 Participants	404.7 meters STANDARD_DEVIATION 80.59 • n=7 Participants	401.1 meters STANDARD_DEVIATION 82.4 • n=5 Participants
World Health Organization (WHO) functional class (FC) II or III at baseline Class II	79 Participants n=5 Participants	78 Participants n=7 Participants	157 Participants n=5 Participants
World Health Organization (WHO) functional class (FC) II or III at baseline Class III	84 Participants n=5 Participants	82 Participants n=7 Participants	166 Participants n=5 Participants
Background PAH Therapy at Baseline Monotherapy	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Background PAH Therapy at Baseline Double therapy	56 Participants n=5 Participants	56 Participants n=7 Participants	112 Participants n=5 Participants
Background PAH Therapy at Baseline Triple therapy	98 Participants n=5 Participants	100 Participants n=7 Participants	198 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and had a baseline value of 6MWD.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 24	34.4 meters Interval 32.5 to 35.5	1.0 meters Interval -1.0 to 5.0

PRIMARY outcome

Timeframe: Up to approximately 24 weeks

Population: All randomized participants who received at least one dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Number of Participants Who Experienced an Adverse Event (AE)	138 Participants	140 Participants

PRIMARY outcome

Timeframe: Up to approximately 24 weeks

Population: All randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Number of Participants Who Discontinued Study Treatment Due to an AE	3 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the multicomponent improvement.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=162 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=159 Participants 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.
Change From Baseline in the Percentage of Participants Achieving Multicomponent Improvement at Week 24	38.9 Percent change	10.1 Percent change

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the PVR.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24	-165.1 dynes*sec/cm^5 Interval -184.0 to -152.0	32.8 dynes*sec/cm^5 Interval 24.0 to 40.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the NT-proBNP levels.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in NT-proBNP Levels at Week 24	-230.3 pg/mL Interval -236.0 to -223.0	58.6 pg/mL Interval 44.0 to 73.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the WHO FC.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=159 Participants 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.
Change From Baseline in the Percentage of Participants Who Improve in WHO FC at Week 24	29.4 Percent change	13.8 Percent change

SECONDARY outcome

Timeframe: Up to approximately 18 months

Population: All randomized participants who received at least one dose of study treatment and who died or experienced a first 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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Time to Death or the First Occurrence of Clinical Worsening Event	NA Weeks Standard Deviation NA 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.	NA Weeks Standard Deviation NA 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.

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline measurement for the low risk score.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=162 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=159 Participants 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.
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	39.5 Percent Change	18.2 Percent Change

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline physical impact domain score.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®) at Week 24	-0.13 Score on a scale Interval -0.15 to 0.0	0.01 Score on a scale Interval 0.0 to 0.14

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline cardiopulmonary domain score.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT® at Week 24	-0.12 Score on a scale Interval -0.14 to -0.06	-0.01 Score on a scale Interval -0.03 to 0.02

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of study treatment and who had a baseline cognitive/emotional impacts domain score.

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.

Outcome measures

Outcome measures
Measure	Sotatercept Plus Background PAH Therapy (DBPC Period) n=163 Participants 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.	Placebo Plus Background PAH Therapy (DBPC Period) n=160 Participants 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.
Change From Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT® at Week 24	0.00 Score on a scale Interval 0.0 to 0.0	0.000007 Score on a scale Interval 0.0 to 0.0006

Adverse Events

Sotatercept Plus Background PAH Therapy (DBPC Period)

Serious events: 23 serious events

Other events: 111 other events

Deaths: 0 deaths

Placebo Plus Background PAH Therapy (DBPC Period)

Serious events: 36 serious events

Other events: 88 other events

Deaths: 6 deaths

Sotatercept Plus Background PAH Therapy (LTDB Period)

Serious events: 26 serious events

Other events: 82 other events

Deaths: 2 deaths

Placebo Plus Background PAH Therapy (LTDB Period)

Serious events: 14 serious events

Other events: 50 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER