Pulmonary Arterial Hypertension
Conditions
Keywords
PAH
Brief summary
This study evaluates the effect of sotatercept (ACE-011) in adults with pulmonary arterial hypertension (PAH). Each eligible participant will receive standard of care (SOC) plus sotatercept (ACE-011) for a 24-week treatment period, followed by an 18-month extension period, and an 8-week follow-up period.
Detailed description
This is a Phase 2a, single-arm, open-label, multicenter exploratory study to determine the effects of sotatercept plus SOC in adults with WHO functional class III PAH. All eligible participants will receive SOC plus sotatercept at a starting dose level of 0.3 mg/kg by subcutaneous (SC) injection for Cycle 1 and escalating to 0.7 mg/kg at Cycle 2 for the remainder of the treatment period. Participants will be required to attend clinic visits once every three weeks for the 24-week treatment period and once every three weeks for the 18-month extension period to perform one or more protocol specified evaluations. Evaluations include hemodynamic measures collected during right heart catheterization (RHC) with invasive cardiopulmonary exercise test (iCPET), and cardiac magnetic resonance imaging (MR), 6-minute walk distance (6MWD), pharmacokinetic parameters, pharmacodynamic parameters, anti-drug antibody testing, and adverse events.
Interventions
BIOLOGICALSotatercept
Sotatercept injection
OTHERSOC
SOC therapy refers to combination therapy consisting of drugs from two or more of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist.
Sponsors
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Documented findings on RHC at any time prior to Screening consistent with a diagnosis of World Health Organization (WHO) pulmonary hypertension Group 1: PAH of any of the following subtypes: * Idiopathic PAH * Heritable PAH * Drug- or toxin-induced PAH * PAH associated with connective tissue disease * 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 III 4. Screening RHC documenting a minimum PVR of ≥ 4 Wood units 5. Pulmonary function tests within 6 months prior to Screening as follows: 1. Total lung capacity \> 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 per investigator interpretation or 2. Forced expiratory volume (first second) (FEV1)/forced vital capacity (FVC) \> 70% predicted 3. For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population-based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility. 6. Ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram \[CTPA\] or pulmonary angiography result), any time prior to Screening or conducted during Screening Period with normal or low probability result 7. 6MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value 8. Combination PAH therapy at stable (per investigator) dose levels for at least 90 days prior to Cycle 1 Day 1 (C1D1)
Exclusion criteria
Participants will be excluded from the study if they meet any of the following criteria: 1. Started or stopped receiving any general supportive therapy for pulmonary hypertension (e.g., diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to C1D1 (Cycle 1 Day 1) 2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to 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. History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C) 6. History of human immunodeficiency virus infection-associated PAH 7. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536) 8. Uncontrolled systemic hypertension as evidenced by sitting systolic BP \> 160 mm Hg or sitting diastolic BP \> 100 mm Hg during Screening after a period of rest 9. Systolic BP \< 90 mm Hg during Screening or at baseline 10. History of known pericardial constriction 11. Electrocardiogram (ECG) with QTcF \> 480 msec during Screening or C1D1 12. History of personal or family history of long QTc syndrome or sudden cardiac death 13. History of restrictive or constrictive cardiomyopathy 14. Left ventricular ejection fraction \< 45% on echocardiogram performed within 6 months of Screening OR pulmonary capillary wedge pressure (PCWP) \> 15 mm Hg on RHC during baseline evaluation 15. Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months prior to Screening) 16. Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment 17. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks | Baseline and 24 weeks | Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks | Baseline and 24 weeks | Each participant's RV ESV was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks | Baseline and 24 weeks | Each participant's RV EDV was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks | Baseline and 24 Weeks | Each participant's RV EF was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks | Baseline and 24 weeks | Each participant's RV SVI was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Change From Baseline in Right Ventricular (RV) Mass at 24 Weeks | Baseline and 24 weeks | Each participant's RV mass was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Change From Baseline in Ventilatory Efficiency (VE/VCO2 Slope) at 24 Weeks | Baseline and 24 weeks | VE/VCO2 slope refers to the slope of the regression line of Minute Ventilation (VE) in liters/minute in the Y-axis and corresponding carbon dioxide production per minute (VCO2) in liters/minute in the X-axis plotted with multiple measurements taken during exercise. Each participant's VE/VCO2 slope at peak exercise was measured by an iCPET at baseline and at 24 weeks. |
| Change From Baseline in Cardiac Index at 24 Weeks | Baseline and 24 weeks | Each participant's cardiac index at peak exercise was measured by iCPET at baseline and at 24 weeks. |
| Change From Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks | Baseline and 24 weeks | Each participant's pulmonary arterial pressure at peak exercise was measured by iCPET at baseline and at 24 weeks. |
| Change From Baseline in Arteriovenous O2 Content Difference (Ca-vO2) at 24 Weeks | Baseline and 24 weeks | Each participant's Ca-vO2 at peak exercise was measured by iCPET at baseline and at 24 weeks. |
| 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 (RHC) at baseline and at 24 weeks. |
| 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 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. |
| 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. |
| Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks | Baseline and 24 weeks | Each participant's RV SV was measured by cardiac MRI at baseline and at 24 weeks. |
| Number of Participants With One or More Adverse Events (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. |
| Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | Up to 102 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). |
| Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9 | Day 1 of Cycle 9 (Each cycle was 21 days.) | Ctrough is the plasma concentration of a drug prior to administration. |
| Maximum Plasma Concentration (Cmax) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmax parameter is derived from this preliminary popPK modeling. |
| Minimum Plasma Concentration (Cmin) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmin parameter is derived from this preliminary popPK modeling. |
| Average Concentration (Cavg) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Cavg is calculated by area under the plasma concentration versus dosing interval time curve at steady-state divided by the dosing interval. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cavg parameter is derived from this preliminary popPK modeling. |
| Area Under the Concentration-Time Curve From 0 to T (AUC0-T) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | AUC0-T (area under the plasma concentration versus time curve from time zero after a dose is given to a period of one 21-day cycle) is a measure of the mean concentration levels of a drug in the plasma at steady state. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The AUC0-T parameter is derived from this preliminary popPK modeling. |
| Apparent Terminal Half-life (t1/2 ) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The t1/2 parameter is derived from this preliminary popPK modeling. |
| Apparent Serum Clearance (CL) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The apparent serum CL parameter is derived from this preliminary popPK modeling. |
| Apparent Volume of Distribution (Vz/F) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Vz/F parameter is derived from this preliminary popPK modeling. |
| Absorption Rate Constant (Ka) of Sotatercept at Cycle 9 | Day 1 of each 21-day cycle: Cycles 1-9 | Ka is the proportionality constant that relates the rate of drug absorbed into the body. Ka is a value used to describe the rate at which a drug enters into the system. It is expressed in units of time. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Ka parameter is derived from this preliminary popPK modeling. |
| Change From Baseline in WHO (World Health Organization) Functional Class at 24 Weeks | Baseline and 24 Weeks | The World Health Organization (WHO) functional class describes how severe a person's pulmonary hypertension symptoms are. There are four different classes - I is the mildest and IV the most severe form of pulmonary hypertension. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sotatercept Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg by subcutaneous (SC) injection during Cycle 1. (Each cycle was 21 days.) From Cycle 2 through Cycle 9, the dose was escalated to 0.7 mg/kg SC. Dosing occurred once every 3 weeks during the 24-week treatment period and 18-month extension period. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Base Study | Withdrawal by Subject | 1 |
| Extension Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sotatercept |
|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 15.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Peak Oxygen Uptake (VO2 max) at Baseline | 11.02 mL/min/kg STANDARD_DEVIATION 3.204 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 |
| other Total, other adverse events | 14 / 21 | 18 / 20 |
| serious Total, serious adverse events | 4 / 21 | 2 / 20 |
Outcome results
Primary
Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks
Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at End Of Treatment (EOT), with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks | 1.28 mL/min/kg | Standard Deviation 2.628 |
Secondary
Absorption Rate Constant (Ka) of Sotatercept at Cycle 9
Ka is the proportionality constant that relates the rate of drug absorbed into the body. Ka is a value used to describe the rate at which a drug enters into the system. It is expressed in units of time. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Ka parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Ka of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Absorption Rate Constant (Ka) of Sotatercept at Cycle 9 | 0.280 1/day | Standard Deviation 0.035 |
Secondary
Apparent Serum Clearance (CL) of Sotatercept at Cycle 9
Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The apparent serum CL parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Apparent Serum CL of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Apparent Serum Clearance (CL) of Sotatercept at Cycle 9 | 0.213 Liters/day | Standard Deviation 0.077 |
Secondary
Apparent Terminal Half-life (t1/2 ) of Sotatercept at Cycle 9
t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The t1/2 parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Apparent t1/2 of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Apparent Terminal Half-life (t1/2 ) of Sotatercept at Cycle 9 | 21.919 Days | Standard Deviation 5.861 |
Secondary
Apparent Volume of Distribution (Vz/F) of Sotatercept at Cycle 9
Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Vz/F parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, and had data for Apparent Vz/F of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Apparent Volume of Distribution (Vz/F) of Sotatercept at Cycle 9 | 3.969 Liters | Standard Deviation 1.078 |
Secondary
Area Under the Concentration-Time Curve From 0 to T (AUC0-T) of Sotatercept at Cycle 9
AUC0-T (area under the plasma concentration versus time curve from time zero after a dose is given to a period of one 21-day cycle) is a measure of the mean concentration levels of a drug in the plasma at steady state. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The AUC0-T parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for AUC0-T of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Area Under the Concentration-Time Curve From 0 to T (AUC0-T) of Sotatercept at Cycle 9 | 172659.953 ng*day/mL | Standard Deviation 57746.622 |
Secondary
Average Concentration (Cavg) of Sotatercept at Cycle 9
Cavg is calculated by area under the plasma concentration versus dosing interval time curve at steady-state divided by the dosing interval. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cavg parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Cavg of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Average Concentration (Cavg) of Sotatercept at Cycle 9 | 8221.907 ng/mL | Standard Deviation 2749.846 |
Secondary
Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
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 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 participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in 6MWD at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | 66.35 meters | Standard Deviation 85.659 |
Secondary
Change From Baseline in Arteriovenous O2 Content Difference (Ca-vO2) at 24 Weeks
Each participant's Ca-vO2 at peak exercise was measured by iCPET at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Ca-vO2 at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Arteriovenous O2 Content Difference (Ca-vO2) at 24 Weeks | 0.63 mL/100 mL | Standard Deviation 2.131 |
Secondary
Change From Baseline in Cardiac Index at 24 Weeks
Each participant's cardiac index at peak exercise was measured by iCPET at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Cardiac Index at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Cardiac Index at 24 Weeks | 0.411 Liter/min/m^2 | Standard Deviation 1.1944 |
Secondary
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 participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and had data for Change from Baseline in Concentration of NT-proBNP at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks | -623.1 pg/mL | Standard Deviation 840.56 |
Secondary
Change From Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks
Each participant's pulmonary arterial pressure at peak exercise was measured by iCPET at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks | -14.9 mmHg | Standard Deviation 13.22 |
Secondary
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks
Each participant's PVR, at resting supine, was measured by right heart catheterization (RHC) at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Change from Baseline in PVR at 24 Weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks | -305.728 dynes*sec/cm^5 | Standard Deviation 313.9827 |
Secondary
Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks
Each participant's RV EDV was measured by cardiac MR imaging at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks | -66.459 mL | Standard Deviation 37.3311 |
Secondary
Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks
Each participant's RV ESV was measured by cardiac MR imaging at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks | -39.151 mL | Standard Deviation 22.5544 |
Secondary
Change From Baseline in Right Ventricular (RV) Mass at 24 Weeks
Each participant's RV mass was measured by cardiac MR imaging at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Right Ventricular (RV) Mass at 24 Weeks | -6.240 grams | Standard Deviation 13.3558 |
Secondary
Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks
Each participant's RV SVI was measured by cardiac MR imaging at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks | -15.073 mL/m^2 | Standard Deviation 14.8219 |
Secondary
Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks
Each participant's RV SV was measured by cardiac MRI at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks | -27.306 mL | Standard Deviation 26.5786 |
Secondary
Change From Baseline in Ventilatory Efficiency (VE/VCO2 Slope) at 24 Weeks
VE/VCO2 slope refers to the slope of the regression line of Minute Ventilation (VE) in liters/minute in the Y-axis and corresponding carbon dioxide production per minute (VCO2) in liters/minute in the X-axis plotted with multiple measurements taken during exercise. Each participant's VE/VCO2 slope at peak exercise was measured by an iCPET at baseline and at 24 weeks.
Time frame: Baseline and 24 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Ventilatory Efficiency (VE/VCO2 Slope) at 24 Weeks | -8.87 Unitless | Standard Deviation 12.298 |
Secondary
Change From Baseline in WHO (World Health Organization) Functional Class at 24 Weeks
The World Health Organization (WHO) functional class describes how severe a person's pulmonary hypertension symptoms are. 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 participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in WHO (World Health Organization) Functional Class at 24 Weeks | -0.76 WHO functional class | Standard Deviation 0.903 |
Secondary
Maximum Plasma Concentration (Cmax) of Sotatercept at Cycle 9
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmax parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment and had at least 1 blood sample analyzed for PK, had data for Cmax of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Maximum Plasma Concentration (Cmax) of Sotatercept at Cycle 9 | 9732.785 ng/mL | Standard Deviation 2852.373 |
Secondary
Minimum Plasma Concentration (Cmin) of Sotatercept at Cycle 9
Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. PopPK modeling approach was used to build a population PK model that captures the totality of the observed data from Cycles 1 to 9. The Cmin parameter is derived from this preliminary popPK modeling.
Time frame: Day 1 of each 21-day cycle: Cycles 1-9
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Cmin of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Minimum Plasma Concentration (Cmin) of Sotatercept at Cycle 9 | 6234.303 ng/mL | Standard Deviation 2466.046 |
Secondary
Number of Participants Who Experienced One or More 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 102 weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations; and who had data for Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of PAH.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotatercept | Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | 1 Participants |
Secondary
Number of Participants With 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 24 weeks
Population: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotatercept | Number of Participants With One or More Adverse Events (AEs) | 20 Participants |
Secondary
Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9
Ctrough is the plasma concentration of a drug prior to administration.
Time frame: Day 1 of Cycle 9 (Each cycle was 21 days.)
Population: All participants who received at least 1 dose of study treatment, had at least 1 blood sample analyzed for PK, had data for Observed Ctrough of Sotatercept at Cycle 9, and followed the dosing regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9 | 5884.79 ng/mL | Standard Deviation 2933.77 |
Secondary
Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks
Each participant's RV EF was measured by cardiac MR imaging at baseline and at 24 weeks.
Time frame: Baseline and 24 Weeks
Population: All participants who completed treatment period, had iCPET assessment and cardiac MRI at 24 weeks or ended treatment early and had iCPET assessment and cardiac MRI at EOT, with no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks | -1.3 Percent change | Standard Deviation 8.48 |