Pulmonary Arterial Hypertension
Conditions
Keywords
PAH
Brief summary
Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH). Eligible participants will receive study treatment for 24 weeks during the placebo-controlled treatment period, and then will be eligible to enroll into a 30-month extension period during which all participants will receive sotatercept. All treated patients will also undergo a follow-up period after last study drug treatment.
Detailed description
This is a Phase 2, double-blind, randomized, placebo-controlled, parallel-group study of sotatercept plus standard of care (SOC) versus placebo plus SOC in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg by subcutaneous (SC) injection every 21 days for a period of 24 weeks in the placebo-controlled treatment period of the study while on SOC therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), quality of life questionnaires, echocardiographic parameters, and safety. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 30-month extension period in which sotatercept-treated participants will receive their latest dose level of sotatercept SC every 21 days and placebo-treated participants will be re-randomized 1:1 to receive sotatercept 0.3 mg/kg SC or sotatercept 0.7 mg/kg SC every 21 days while on SOC therapy.
Interventions
DRUGPlacebo
Placebo
DRUGSotatercept
Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1.
OTHERSOC
SOC therapy refers to approved PAH-specific medications and may consist of monotherapy or combination therapy with endothelin-receptor antagonists, phosphodiesterase 5 (PDE5) inhibitors, soluble guanylate cyclase stimulators, and/or prostacyclin analogues or receptor agonists.
Sponsors
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Documented diagnostic right heart catheterization (RHC) at any time prior to Screening confirming diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH in any of the following subtypes: i. Idiopathic ii. Heritable PAH iii. Drug- or toxin-induced PAH iv. PAH associated with connective tissue disease v. PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair 3. Symptomatic pulmonary hypertension classified as WHO functional class II or III 4. Screening RHC documenting a minimum PVR of ≥400 dyn·sec/cm5 (5 Wood units) 5. Pulmonary function tests (PFTs) within 6 months prior to Screening as follows: 1. Total lung capacity (TLC) \>70% predicted; or if between 60 to 70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease (ILD), per investigator interpretation, or 2. Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) \>70% predicted 6. Ventilation-perfusion (VQ) scan (or, if unavailable a negative CT pulmonary angiogram \[CTPA\] result, or pulmonary angiography result), any time prior to Screening Visit or conducted during the Screening Period, with normal or low probability result), 7. No contraindication per investigator for RHC during the study 8. 6MWD ≥150 and ≤550 meters repeated twice at Screening and both values within 15% of each other, calculated from the highest value 9. PAH therapy at stable (per investigator) dose levels of SOC therapies
Exclusion criteria
1. Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit Cycle 1 Day 1 (C1D1) 2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to study visit C1D1 3. History of atrial septostomy within 180 days prior to Screening 4. History of more than mild obstructive sleep apnea that is untreated 5. 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) 6. History of human immunodeficiency virus infection-associated PAH 7. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536) 8. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to C1D1 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). 9. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) \>160 mm Hg or sitting diastolic blood pressure \>100 mm Hg during Screening Visit after a period of rest 10. Systolic BP \<90 mmHg during Screening or at baseline 11. History of known pericardial constriction 12. Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) \>480 msec during Screening Period or C1D1 13. Personal or family history of long QTc syndrome or sudden cardiac death 14. Cerebrovascular accident within 3 months of C1D1 15. History of restrictive or congestive cardiomyopathy 16. Left ventricular ejection fraction (LVEF) \<45% on historical echocardiogram (ECHO) within 6 months prior to Screening Period (or done as a part of the Screening Period) or pulmonary capillary wedge pressure (PCWP) \>15 mmHg as determined in the Screening Period RHC. 17. Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) 18. Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment 19. Significant (≥2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation (AR) valvular disease 20. Any of the following clinical laboratory values during the Screening Period prior to C1D1: 1. Baseline Hgb \>16.0 g/dL 2. Serum alanine aminotransferase or aspartate aminotransferase levels \>3X upper limit of normal (ULN) or total bilirubin \>1.5X ULN within 28 days of C1D1 3. Estimated glomerular filtration rate \<30 ml/min/1.73m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of C1D1 or required renal replacement therapy within 90 days 4. WBC count \<4000/mm3 5. Platelets \<100,000/μL 6. Absolute neutrophil count \<1500/mm3 21. History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia) within 6 months prior to Screening; serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening 22. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product 23. Major surgery within 8 weeks prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1. 24. Prior heart or heart-lung transplants or life expectancy of \<12 month 25. Pregnant or breastfeeding females 26. If on corticosteroids, and at any time in the last 30 days prior to the Screening Period: have been receiving doses of \>20 mg/day of prednisone (or equivalent) or on a new or changing dose of ≤20 mg/day; only participants receiving stable doses of ≤20 mg prednisone (or equivalent) in last 30 days prior to the Screening Period permitted in the study 27. History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤2 squamous cell carcinomas of the skin 28. History of clinically significant (as determined by the investigator) non-PAH related cardiac, endocrine, hematologic, hepatic, (auto)immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study. Autoimmune diseases are excluded with the exception of those related to PAH etiologies included in this study. 29. Participation in another clinical trial involving intervention with another investigational drug, approved therapy for investigational use, or investigational device within 4 weeks prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer 30. Weight \>140 kg at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Baseline and 24 weeks | Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and at 24 weeks. |
| Extension Period: Change From Baseline in PVR (Delayed-Start Analysis) | Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24 | Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24. |
| Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis) | Baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24. | Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24. |
| Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to approximately 32 months | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE | Up to 30 months | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | The SF-36 questionnaire is a participant-reported survey of a participant's health. The survey evaluates 8 aspects of functional health and well-being that relate to either physical health or mental health. The physical component summary is based primarily on physical functioning, bodily pain, and general health. The mental component summary encompasses vitality, social functioning, and emotional and mental health. Total scores for the physical component range from 0-100, with 100 representing the highest level of physical functioning. The total scores for the mental component also range from 0-100, with 100 representing the highest level of mental functioning. Each participant's SF-36 was recorded at baseline and on Day 1 of Cycle 9. Each cycle was 21 days. |
| Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks | Baseline and 24 Weeks | The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. |
| Base Study: Number of Participants Who Experienced One or More AEs | Up to 24 weeks | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE | Up to 24 weeks | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9 | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | Each participant's BMI was measured at baseline and at 24 weeks. |
| Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | Each participant's systolic and diastolic blood pressure was taken at baseline and on Day 1 of Cycle 9. Each cycle was 21 days. |
| Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | Baseline and 24 weeks | 6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in basic mobility. |
| Base Study: Change From Baseline in QTcF Interval at Cycle 9 | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | Each participant's QTcF Interval was measured at baseline and on Day 1 of Cycle 9. |
| Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept | Day 8 of Cycle 1 (Each cycle was 21 days.) | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Based on population pharmacokinetic (PopPK) modeling of previous sotatercept studies, Cmax occurs at Day 8 of Cycle 1 after a sotatercept dose is given. The sotatercept concentration at Day 8 of Cycle 1 (each cycle was 21 days) is presented here as Cmax. |
| Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis) | Baseline and the timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24 | 6MWD is measured by an exercise test known as 6MWT that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and the timepoint at which the third RCH was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility. |
| Extension Period: Change From Baseline in 6MWD (Placebo-Crossed Analysis) | Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24 | 6MWD is measured by an exercise test known as 6MWT that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility. |
| Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis) | Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24 | The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed. |
| Extension Period: Change From Baseline in WHO Functional Class (Placebo-Crossed Analysis) | Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24 | The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed. |
| Base Study: Change From Baseline in Respiratory Rate at Cycle 9 | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | Each participant's respiratory rate (number of breaths per minute) was measured at baseline and on Day 1 of Cycle 9. Each cycle was 21 days. |
| Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks | Baseline and 24 Weeks | Each participant's laboratory biomarkers N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP) were measured at baseline and at 24 weeks. |
| Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | Up to 24 weeks | Events that indicate clinical worsening of PAH include death, need for and/or worsening-related listing for lung and/or heart transplant, need to initiate an approved PAH SOC rescue therapy, PAH-specific hospitalization, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD). |
| Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks | Baseline and 24 weeks | Each participant's TAPSE, which is commonly used to evaluate tricuspid valve annulus movement as an indicator of right heart function, was measured by echocardiography at baseline and 24 weeks. |
| Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9 | Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.) | The CAMPHOR is participant-reported questionnaire that contains 65 items in total, 25 relating to symptoms, 25 relating to quality of life (QoL), and 15 relating to activities. Symptom items are scored from 0-25, with a higher score indicating worse symptoms. QoL items are also scored from 0-25, with a higher score indicating a worse QoL and greater functional limitation. Activity items are scored from 0-30, with a higher score indicating poorer functioning. The combined score is obtained by summing up the symptoms score, QoL score and activity score. The lowest combined score possible is 0, while the highest combined score possible is 80. Each participant's CAMPHOR score was recorded at baseline and on Day 1 of Cycle 9. |
Countries
Australia, Brazil, France, Germany, Israel, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo plus SOC by SC injection during the 24-week treatment period (Base Study; Cycles 1-8). Each cycle was 21 days. Dosing occurred once every 3 weeks. | 32 |
| Sotatercept 0.3 mg/kg Participants received sotatercept 0.3 mg/kg plus SOC by SC injection during the 24-week treatment period (Base Study; Cycles 1-8) and 30-month extension period (Cycles 9-51). Each cycle was 21 days. Dosing occurred once every 3 weeks. | 32 |
| Sotatercept 0.7 mg/kg Participants received sotatercept 0.7 mg/kg plus SOC by SC injection during the 24-week treatment period (Base Study; Cycles 1-8) and 30-month extension period (Cycles 9-51). Each cycle was 21 days. Dosing occurred once every 3 weeks. | 42 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Base Study | Adverse Event | 0 | 0 | 1 | 1 | 4 |
| Base Study | Death | 0 | 0 | 0 | 0 | 1 |
| Base Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 |
| Extension Period | Adverse Event | 0 | 0 | 0 | 1 | 1 |
| Extension Period | Death | 1 | 0 | 0 | 1 | 2 |
| Extension Period | Elevated hemoglobin levels | 0 | 0 | 0 | 0 | 1 |
| Extension Period | Withdrawal by Subject | 1 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Sotatercept 0.3 mg/kg | Sotatercept 0.7 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 45.6 Years STANDARD_DEVIATION 13.38 | 49.1 Years STANDARD_DEVIATION 14.34 | 49.8 Years STANDARD_DEVIATION 15.05 | 48.3 Years STANDARD_DEVIATION 14.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 9 Participants | 13 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 28 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 30 Participants | 31 Participants | 37 Participants | 98 Participants |
| Sex: Female, Male Female | 26 Participants | 29 Participants | 37 Participants | 92 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 1 / 42 | 1 / 15 | 0 / 15 | 1 / 32 | 2 / 42 |
| other Total, other adverse events | 25 / 32 | 29 / 32 | 33 / 42 | 14 / 15 | 15 / 15 | 30 / 31 | 36 / 36 |
| serious Total, serious adverse events | 3 / 32 | 2 / 32 | 10 / 42 | 6 / 15 | 4 / 15 | 10 / 31 | 12 / 36 |
Outcome results
Primary
Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All randomized participants administered their assigned treatment who received at least 6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and End of Treatment (EOT) assessment. Note: Data from participants whose dose was down-titrated were analyzed according to dose received at least 6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Base Study: Change from Baseline in PVR at 24 Weeks | -27.6 dynes*sec/cm^5 | Standard Deviation 251.08 |
| Placebo | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Baseline | 802.0 dynes*sec/cm^5 | Standard Deviation 331.05 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Base Study: Change from Baseline in PVR at 24 Weeks | -168.4 dynes*sec/cm^5 | Standard Deviation 262.93 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Baseline | 772.0 dynes*sec/cm^5 | Standard Deviation 285.62 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Base Study: Change from Baseline in PVR at 24 Weeks | -258.9 dynes*sec/cm^5 | Standard Deviation 169.42 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | Baseline | 715.5 dynes*sec/cm^5 | Standard Deviation 267.11 |
Comparison: Analysis based on calculated LS means.p-value: 0.00395% CI: [-249.59, -52.63]ANCOVA
Comparison: Analysis based on calculated LS means.p-value: <0.000195% CI: [-365.81, -173.03]ANCOVA
Primary
Extension Period: Change From Baseline in PVR (Delayed-Start Analysis)
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for the respective timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extension Period: Change From Baseline in PVR (Delayed-Start Analysis) | Extension Period: Change from Baseline in PVR (Delayed-Start Analysis) | -246.9 dynes*sec/cm^5 | Standard Deviation 300.01 |
| Placebo | Extension Period: Change From Baseline in PVR (Delayed-Start Analysis) | Baseline | 802.0 dynes*sec/cm^5 | Standard Deviation 331.05 |
| Sotatercept 0.3 mg/kg | Extension Period: Change From Baseline in PVR (Delayed-Start Analysis) | Extension Period: Change from Baseline in PVR (Delayed-Start Analysis) | -212.6 dynes*sec/cm^5 | Standard Deviation 254.24 |
| Sotatercept 0.3 mg/kg | Extension Period: Change From Baseline in PVR (Delayed-Start Analysis) | Baseline | 783.7 dynes*sec/cm^5 | Standard Deviation 371.59 |
Comparison: Analysis based on calculated LS means.p-value: 0.785195% CI: [-113.85, 86.06]ANCOVA
Primary
Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis)
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Time frame: Baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for the respective timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis) | Extension Period: Change from Baseline in PVR (Placebo-Crossed Analysis) | -246.9 dynes*sec/cm^5 | Standard Deviation 300.01 |
| Placebo | Extension Period: Change From Baseline in PVR (Placebo-Crossed Analysis) | Baseline | 802.0 dynes*sec/cm^5 | Standard Deviation 331.05 |
p-value: <0.000195% CI: [-335.83, -110.49]ANCOVA
Primary
Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 30 months
Population: All randomized participants who transitioned to the extension period and received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Sotatercept 0.3 mg/kg | Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Sotatercept 0.7 mg/kg | Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Extension Period: Sotatercept 0.7 mg/kg | Extension Period: Number of Participants Who Discontinued Study Treatment Due to an AE | 3 Participants |
Primary
Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to approximately 32 months
Population: All randomized participants who transitioned to the extension period and received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs) | 14 Participants |
| Sotatercept 0.3 mg/kg | Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs) | 15 Participants |
| Sotatercept 0.7 mg/kg | Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs) | 31 Participants |
| Extension Period: Sotatercept 0.7 mg/kg | Extension Period: Number of Participants Who Experienced One or More Adverse Events (AEs) | 36 Participants |
Secondary
Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score
The SF-36 questionnaire is a participant-reported survey of a participant's health. The survey evaluates 8 aspects of functional health and well-being that relate to either physical health or mental health. The physical component summary is based primarily on physical functioning, bodily pain, and general health. The mental component summary encompasses vitality, social functioning, and emotional and mental health. Total scores for the physical component range from 0-100, with 100 representing the highest level of physical functioning. The total scores for the mental component also range from 0-100, with 100 representing the highest level of mental functioning. Each participant's SF-36 was recorded at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants administered their assigned treatment who received ≥6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment, and had data for the outcome measure. Note: Data from participants whose dose was down-titrated were analyzed according to dose received ≥6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Physical component | 3.5 Score on a scale | Standard Error 1.07 |
| Placebo | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Mental component | 3.2 Score on a scale | Standard Error 1.33 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Physical component | 4.5 Score on a scale | Standard Error 1.12 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Mental component | 3.6 Score on a scale | Standard Error 1.39 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Physical component | 3.1 Score on a scale | Standard Error 1.11 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score | Mental component | 0.0 Score on a scale | Standard Error 1.4 |
Secondary
Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.
Time frame: Baseline and 24 weeks
Population: All randomized participants administered their assigned treatment who received at least 6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment. Note: Data from participants whose dose was down-titrated were analyzed according to dose received at least 6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | 31.4 meters | Standard Error 9.69 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | 56.0 meters | Standard Error 10.07 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | 53.6 meters | Standard Error 9.84 |
Secondary
Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9
Each participant's BMI was measured at baseline and at 24 weeks.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants who received their assigned treatment and had data for Base Study: Change from Baseline in BMI at Cycle 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9 | -0.2 kg/m^2 | Standard Deviation 1.25 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9 | 0.6 kg/m^2 | Standard Deviation 0.89 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Body Mass Index (BMI) at Cycle 9 | 0.2 kg/m^2 | Standard Deviation 1.07 |
Secondary
Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9
The CAMPHOR is participant-reported questionnaire that contains 65 items in total, 25 relating to symptoms, 25 relating to quality of life (QoL), and 15 relating to activities. Symptom items are scored from 0-25, with a higher score indicating worse symptoms. QoL items are also scored from 0-25, with a higher score indicating a worse QoL and greater functional limitation. Activity items are scored from 0-30, with a higher score indicating poorer functioning. The combined score is obtained by summing up the symptoms score, QoL score and activity score. The lowest combined score possible is 0, while the highest combined score possible is 80. Each participant's CAMPHOR score was recorded at baseline and on Day 1 of Cycle 9.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants administered their assigned treatment who received ≥6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment, and had data for the outcome measure. Note: Data from participants whose dose was down-titrated were analyzed according to dose received ≥6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9 | -10.2 Score on a scale | Standard Deviation 12.91 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9 | -6.9 Score on a scale | Standard Deviation 12.51 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Score at Cycle 9 | -7.5 Score on a scale | Standard Deviation 7.96 |
Secondary
Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks
Each participant's laboratory biomarkers N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP) were measured at baseline and at 24 weeks.
Time frame: Baseline and 24 Weeks
Population: All randomized participants administered their assigned treatment who received ≥6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment, and had data for the outcome measure. Note: Data from participants whose dose was down-titrated were analyzed according to dose received ≥6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks | 195.9 pg/mL | Standard Deviation 726.46 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks | -718.2 pg/mL | Standard Deviation 965.12 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks | -359.0 pg/mL | Standard Deviation 757.58 |
Secondary
Base Study: Change From Baseline in QTcF Interval at Cycle 9
Each participant's QTcF Interval was measured at baseline and on Day 1 of Cycle 9.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants who received their assigned treatment and had data for Base Study: Change from Baseline in QTcF Interval at Cycle 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in QTcF Interval at Cycle 9 | 0.7 milliseconds | Standard Deviation 31.1 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in QTcF Interval at Cycle 9 | -7.4 milliseconds | Standard Deviation 20.57 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in QTcF Interval at Cycle 9 | -9.1 milliseconds | Standard Deviation 31.55 |
Secondary
Base Study: Change From Baseline in Respiratory Rate at Cycle 9
Each participant's respiratory rate (number of breaths per minute) was measured at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants who received their assigned treatment and had data for Base Study: Change from Baseline in Respiratory Rate at Cycle 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Respiratory Rate at Cycle 9 | -0.3 breaths/min | Standard Deviation 2.1 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Respiratory Rate at Cycle 9 | -1.3 breaths/min | Standard Deviation 3.72 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Respiratory Rate at Cycle 9 | -0.3 breaths/min | Standard Deviation 3.05 |
Secondary
Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9
Each participant's systolic and diastolic blood pressure was taken at baseline and on Day 1 of Cycle 9. Each cycle was 21 days.
Time frame: Baseline and Day 1 of Cycle 9, up to 24 weeks (Each cycle was 21 days.)
Population: All randomized participants who received their assigned treatment and had data for Base Study: Change from Baseline in Systolic and Diastolic Blood Pressure at Cycle 9
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Systolic blood pressure | -0.8 mmHg | Standard Deviation 10.06 |
| Placebo | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Diastolic blood pressure | 2.3 mmHg | Standard Deviation 8.06 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Systolic blood pressure | 3.4 mmHg | Standard Deviation 11.75 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Diastolic blood pressure | 4.1 mmHg | Standard Deviation 8.64 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Systolic blood pressure | 2.6 mmHg | Standard Deviation 12.28 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Systolic and Diastolic Blood Pressure at Cycle 9 | Diastolic blood pressure | 1.7 mmHg | Standard Deviation 8.69 |
Secondary
Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks
Each participant's TAPSE, which is commonly used to evaluate tricuspid valve annulus movement as an indicator of right heart function, was measured by echocardiography at baseline and 24 weeks.
Time frame: Baseline and 24 weeks
Population: All randomized participants administered their assigned treatment who received ≥6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment, and had data for the outcome measure. Note: Data from participants whose dose was down-titrated were analyzed according to dose received ≥6 times rather than dose originally assigned. Per protocol, only participants who consistently received in 0.3 mg/kg or 0.7 mg/kg of sotatercept were planned to be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks | 0.0 cm | Standard Deviation 0.39 |
| Sotatercept 0.3 mg/kg | Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks | 0.1 cm | Standard Deviation 0.26 |
| Sotatercept 0.7 mg/kg | Base Study: Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at 24 Weeks | -0.1 cm | Standard Deviation 0.34 |
Secondary
Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Based on population pharmacokinetic (PopPK) modeling of previous sotatercept studies, Cmax occurs at Day 8 of Cycle 1 after a sotatercept dose is given. The sotatercept concentration at Day 8 of Cycle 1 (each cycle was 21 days) is presented here as Cmax.
Time frame: Day 8 of Cycle 1 (Each cycle was 21 days.)
Population: All randomized participants who received at least 1 dose of sotatercept and had sufficient pharmacokinetic samples collected and assayed for PK analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept | 1910.3 ng/mL | Standard Deviation 715.86 |
| Sotatercept 0.3 mg/kg | Base Study: Maximum Plasma Concentration (Cmax) of Sotatercept | 4598.5 ng/mL | Standard Deviation 1622.59 |
Secondary
Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Sotatercept 0.3 mg/kg | Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Sotatercept 0.7 mg/kg | Base Study: Number of Participants Who Discontinued Study Treatment Due to an AE | 5 Participants |
Secondary
Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension.
Time frame: Baseline and 24 Weeks
Population: All randomized participants who received their assigned treatment and at least 6 of the same doses during Base Study, had baseline and post-Base Study PVR assessment and EOT assessment, and had data for Base Study: Number of Participants Who Experienced an Improvement from Baseline in WHO Functional Class at 24 Weeks. Note: Data from participants whose dose was down-titrated were analyzed according to dose received at least 6 times rather than dose to which originally assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks | 4 Participants |
| Sotatercept 0.3 mg/kg | Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks | 8 Participants |
| Sotatercept 0.7 mg/kg | Base Study: Number of Participants Who Experienced an Improvement From Baseline in World Health Organization (WHO) Functional Class at 24 Weeks | 6 Participants |
Secondary
Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH)
Events that indicate clinical worsening of PAH include death, need for and/or worsening-related listing for lung and/or heart transplant, need to initiate an approved PAH SOC rescue therapy, PAH-specific hospitalization, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD).
Time frame: Up to 24 weeks
Population: All randomized participants who received their assigned treatment and had data for Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of PAH
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | 2 Participants |
| Sotatercept 0.3 mg/kg | Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | 0 Participants |
| Sotatercept 0.7 mg/kg | Base Study: Number of Participants Who Experienced Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | 1 Participants |
Secondary
Base Study: Number of Participants Who Experienced One or More AEs
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Base Study: Number of Participants Who Experienced One or More AEs | 29 Participants |
| Sotatercept 0.3 mg/kg | Base Study: Number of Participants Who Experienced One or More AEs | 29 Participants |
| Sotatercept 0.7 mg/kg | Base Study: Number of Participants Who Experienced One or More AEs | 35 Participants |
Secondary
Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis)
6MWD is measured by an exercise test known as 6MWT that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and the timepoint at which the third RCH was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.
Time frame: Baseline and the timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for Extension Period: Change from Baseline in 6MWD (Delayed-Start Analysis)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis) | 60.1 meters | Standard Error 14.35 |
| Sotatercept 0.3 mg/kg | Extension Period: Change From Baseline in 6MWD (Delayed-Start Analysis) | 55.7 meters | Standard Error 9.47 |
Secondary
Extension Period: Change From Baseline in 6MWD (Placebo-Crossed Analysis)
6MWD is measured by an exercise test known as 6MWT that assesses aerobic capacity and endurance. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in performance capacity. Each participant's 6MWD was measured at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's 6MWD was also measured. An increase in the distance walked during the 6MWT indicates improvement in basic mobility.
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for Extension Period: Change from Baseline in 6MWD (Placebo-Crossed Analysis)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extension Period: Change From Baseline in 6MWD (Placebo-Crossed Analysis) | 60.5 meters | Standard Error 13.21 |
Secondary
Extension Period: Change From Baseline in WHO Functional Class (Placebo-Crossed Analysis)
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed.
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for Extension Period: Change from Baseline in WHO Functional Class (Placebo-Crossed Analysis)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extension Period: Change From Baseline in WHO Functional Class (Placebo-Crossed Analysis) | -0.6 WHO functional class | Standard Deviation 0.74 |
Secondary
Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis)
The WHO Functional Class describes the severity of a person's pulmonary hypertension symptoms. There are four different classes: I is the mildest and IV the most severe form of pulmonary hypertension. Each participant's WHO Functional Class was assessed at baseline and the timepoint at which the third right heart catheterization was performed. This occurred between Month 18 and Month 24, at which time each participant's WHO Functional Class was also assessed.
Time frame: Baseline and timepoint at which third right heart catheterization was performed, which occurred between Month 18 and Month 24
Population: All randomized participants who received their assigned treatment, transitioned to the extension period, and had data for Extension Period: Number of Participants Who Experienced an Improvement from Baseline in WHO Functional Class (Delayed-Start Analysis)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis) | 16 Participants |
| Sotatercept 0.3 mg/kg | Extension Period: Number of Participants Who Experienced an Improvement From Baseline in WHO Functional Class (Delayed-Start Analysis) | 27 Participants |