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| ID | Type | Description | Link |
|---|---|---|---|
| 7962-002 | Other Identifier | Merck |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sotatercept | Experimental | Each participant will receive SOC plus sotatercept at a dose of 0.3 mg/kg SC for Cycle 1. (Each cycle will be 21 days.) From Cycle 2 through Cycle 9, the dose will be escalated to 0.7 mg/kg SC. Dosing will be every three weeks during the 24-week treatment period and 18-month extension period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sotatercept | Biological | Sotatercept injection |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 24 weeks |
| Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks |
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Inclusion Criteria:
Age ≥ 18 years
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:
Symptomatic pulmonary hypertension classified as WHO functional class III
Screening RHC documenting a minimum PVR of ≥ 4 Wood units
Pulmonary function tests within 6 months prior to Screening as follows:
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
6MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value
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:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Jonathan Lu, MD | Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Arizona | Tucson | Arizona | 85724 | United States | ||
| Brigham and Women's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38572639 | Result | Waxman AB, Systrom DM, Manimaran S, de Oliveira Pena J, Lu J, Rischard FP. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension. Circ Heart Fail. 2024 May;17(5):e011227. doi: 10.1161/CIRCHEARTFAILURE.123.011227. Epub 2024 Apr 4. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
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| Base Study |
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| Extension Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | mL/min/kg | Baseline and 24 weeks |
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Treatment period: Up to 24 weeks; Extension period: Up to 18 months plus 8-week follow-up period.
The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sotatercept Treatment Period | Each participant received standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg SC during Cycle 1. (Each cycle was 21 days.) For the remainder of the 24-week treatment period (Cycle 2 through Cycle 9), participants received an escalated dose of 0.7 mg/kg SC. Dosing occurred once every 3 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haematochezia | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Polycythaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 12, 2021 | Dec 20, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C542017 | ACE-011 |
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| SOC | Other | 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. |
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Each participant's RV ESV was measured by cardiac MR imaging at baseline and at 24 weeks. |
| Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 Weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 weeks |
| 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. | Baseline and 24 Weeks |
| 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. | Baseline and 24 Weeks |
| 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. | Up to 24 weeks |
| 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). | Up to 102 weeks |
| Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9 | Ctrough is the plasma concentration of a drug prior to administration. | Day 1 of Cycle 9 (Each cycle was 21 days.) |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| 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. | Day 1 of each 21-day cycle: Cycles 1-9 |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Peak Oxygen Uptake (VO2 max) at Baseline | Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline. | All participants who completed treatment period, had iCPET assessment and cardiac magnetic resonance imaging (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. | Mean | Standard Deviation | mL/min/kg |
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| 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. | 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. | Posted | Mean | Standard Deviation | mL | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | mL | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | mL | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | Percent change | Baseline and 24 Weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | mL/m^2 | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | grams | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | Unitless | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liter/min/m^2 | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | mL/100 mL | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | dynes*sec/cm^5 | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | meters | Baseline and 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | pg/mL | Baseline and 24 Weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | WHO functional class | Baseline and 24 Weeks |
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| 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. | All participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 24 weeks |
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| 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). | 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. | Posted | Count of Participants | Participants | Up to 102 weeks |
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| Secondary | Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9 | Ctrough is the plasma concentration of a drug prior to administration. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 of Cycle 9 (Each cycle was 21 days.) |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng*day/mL | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Days | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters/day | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters | Day 1 of each 21-day cycle: Cycles 1-9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | 1/day | Day 1 of each 21-day cycle: Cycles 1-9 |
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|
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| 0 |
| 21 |
| 4 |
| 21 |
| 14 |
| 21 |
| EG001 | Sotatercept Extension Period | Each participant received standard of care (SOC) plus sotatercept at a dose of 0.7 mg/kg SC once every 3 weeks during the 18-month extension period. | 0 | 20 | 2 | 20 | 18 | 20 |
| Complication associated with device | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Hypervolaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
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| Device leakage | Product Issues | MedDRA 25.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Complication associated with device | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 25.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
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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.