This is a Phase 2, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of sotatercept versus placebo in adults with Cpc-PH due to HFpEF. The objective of this study is to evaluate the efficacy, safety and tolerability of sotatercept versus placebo in adults with Cpc-PH due to HFpEF. Efficacy is measured by change from baseline in pulmonary vascular resistance (PVR, primary endpoint) and 6-minute walk distance (6MWD, key secondary endpoint).
Participants enrolled in the study will have a diagnosis of Cpc-PH due to HFpEF with New York Heart Association (NYHA) functional class (FC) II or III. Participants will be randomly assigned in a 1:1:1 ratio to 1 of the 3 treatment groups (placebo, 0.3mg/kg sotatercept and 0.7mg/kg sotatercept) during the placebo-controlled Treatment Period. In the extension phase, sotatercept-treated participants will continue on their current dose. Placebo participants will be re-randomized in a 1:1 ratio to one of the two sotatercept treatment groups utilized in the placebo-controlled Treatment Period. Each participant will be enrolled in the study for up to 114 weeks, including a 28-day Screening Period, a 24-week, double-blind, placebo-controlled Treatment Period, an 18-month Extension Period, and an 8-week Follow-up Period. As of protocol amendment 6, the 18-month Extension Period is being removed. Participants who have completed at least the 24-week placebo controlled treatment period and the end of study visit, and who have not discontinued study treatment early, may be eligible to participate in an extension study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
164
Administered by subcutaneous injection. 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.
Administered by subcutaneous injection
Administered by subcutaneous injection. 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.
PULMONARY ASSOCIATES, P.A. ( Site 1008)
Phoenix, Arizona, United States
University of Arizona ( Site 1006)
Tucson, Arizona, United States
Scripps Clinic ( Site 4001)
La Jolla, California, United States
Cedars Sinai Medical Center ( Site 1082)
Los Angeles, California, United States
University of California Irvine ( Site 1086)
Orange, California, United States
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24
PVR, a hemodynamic variable of pulmonary circulation, is measured by right heart catheterization (RHC).
Time frame: Baseline and Week 24
Change From Baseline in the 6-Minute Walk Distance (6MWD) at Week 24
The 6MWD tests the distance walked in 6 minutes as a measure of functional capacity.
Time frame: Baseline and Week 24
Time to First Clinical Worsening Event (TTCW) at Weeks 24
Clinical Worsening events are defined as the number of weeks from first dose date to any of the following: * Hospitalization due to a cardiopulmonary indication (a non-elective hospitalization lasting at least 24 hours in duration caused by clinical conditions directly related to Pulmonary Hypertension and/or Heart Failure) * Administration of intravenous diuretics or subcutaneous (SC) furosemide * Death (all causes) * Decrease in 6 minute walk distance (6MWD) by ≥ 15% from baseline confirmed by 2 tests at least 4 hours, but no more than 1 week apart.
Time frame: Week 24
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24
mPAP is calculated from systolic and diastolic pulmonary artery pressure measured by right heart catheterization.
Time frame: Baseline and Week 24
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 24
PCWP is an indirect estimate of left atrial pressure measured in right heart catheterization.
Time frame: Baseline and Week 24
Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 24
TAPSE is an echocardiographic measurement of tricuspid valve annulus movement, as an indicator of right heart function.
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular Fractional Area Change (RVFAC) at Week 24
RVFAC is an echocardiographic measurement of percent change between right ventricular area during diastole and systole, as an indicator of right heart function.
Time frame: Baseline and Week 24
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24
LVEF is an echocardiographic measurement of percent change between left ventricular volume during diastole and systole, as an indicator of left heart function.
Time frame: Baseline and Week 24
Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 24
IVRT is an echocardiographic measurement of the interval between closure of the aortic valve, to onset of filling by opening of the mitral valve. It is used as an indicator of diastolic dysfunction.
Time frame: Baseline and Week 24
Change From Baseline in ratio of mitral inflow velocity I to mitral annular velocity'(e') (E/e' ratio) at Week 24
E/e' is a ratio measured in echocardiography as an indicator of diastolic function.
Time frame: Baseline and Week 24
Change From Baseline in the Ratio of the Peak Velocity Flow of the E Wave in Early Diastole to Peak Velocity Flow of the A Wave in Late Diastole (E/A Ratio) at Week 24
E/A is a ratio measured in echocardiography as an indicator of diastolic function.
Time frame: Baseline and Week 24
Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) at Week 24
NT-proBNP is a circulating biomarker that reflects myocardial stretch.
Time frame: Baseline and Week 24
Change From Baseline in New York Heart Association Functional Class (NYHA FC) at Week 24
NYHA FC classifies the extent of heart failure.
Time frame: Baseline and Week 24
Change From Baseline in Myocardial Contraction Fraction (MCF) at Week 24
MCF is an echocardiographic measurement that determines the ratio of left ventricular stroke volume to myocardial volume and is an indicator of left ventricular systolic function.
Time frame: Baseline and Week 24
Percentage of Participants with One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
Time frame: Week 24
Percentage of Participants who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
Time frame: Week 24
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Jeffrey S.Sager MD Medical Corporation ( Site 1060)
Santa Barbara, California, United States
Stanford University ( Site 1024)
Stanford, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)
Torrance, California, United States
University Of Colorado ( Site 1013)
Aurora, Colorado, United States
South Denver Cardiology Associates ( Site 1091)
Littleton, Colorado, United States
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