Pulmonary Arterial Hypertension (PAH) MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Acceleron Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of WHO pulmonary arterial hypertension (PAH) Group 1 in any of the following subtypes: • Idiopathic PAH • Heritable PAH • Drug/toxin-induced PAH • PAH associated with connective tissue disease • PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair 3. Symptomatic pulmonary hypertension classified as WHO Functional Class II or III 4. Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of = 5 WU 5. At stable doses of background PAH therapy and diuretics (i.e., patientspecific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice. 6. 6MWD = 150 and = 500 m repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value) 7. Females of childbearing potential must: • Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug • If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment • Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment 8. Male participants must: • Agree to use a condom, defined as a male latex condom or non-latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy • Refrain from donating blood or sperm for the duration of the study and for 112 days (112 days) after the last dose of study treatment 9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements 10. Ability to understand and provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 142 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 142
Exclusion criteria
Exclusion criteria: 1. Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5 2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension. Exclusions in PAH Group I should also include schistosomiasis APAH and pulmonary veno-occlusive disease 3. Hemoglobin (Hgb) at screening above gender-specific upper limit of normal, per local laboratory test 4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mmHg or sitting diastolic blood pressure > 100 mmHg during screening visit after a period of rest 5. Baseline systolic BP 3 × upper limit of normal (ULN) or total bilirubin > 1.5 × ULN 8. Currently enrolled in or have completed any other investigational product study within 30 days for small-molecule drugs or within 5 halflives for biologics prior to the date of signed informed consent 9. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536) or known allergic reaction to either one 10. Have full or partial pneumonectomy 11. Pulmonary function test (PFT) values of forced vital capacity (FVC) 500 ms during screening visit 18. Personal or family history of long QT syndrome (LQTS) or sudden cardiac death 19. Left ventricular ejection fraction (LVEF) 15 mmHg as determined in the Screening Period RHC 20. 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) in the past 6 months prior to the screening visit. Note: Anginal pain can be ignored as an exclusion criterion if coronary angiography shows no obstructions 21. Cerebrovascular accident within 3 months prior to the screening visit 22. Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment 23. Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease. 24. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of this study are to evaluate the efficacy and safety of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) at 24 weeks in adults with PAH.;Secondary Objective: Not Applicable;Primary end point(s): The primary efficacy endpoint is the change from baseline in 6MWD;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Multicomponent improvement endpoint measured by the proportion of participants achieving all of the following: • Improvement in NT-proBNP (decrease in NT-proBNP = 30%) or maintenance/achievement of NT-proBNP level < 300 ng/L • Improvement in WHO FC or maintenance of WHO FC II 2. Change from baseline in PVR 3. Change from baseline in NT-proBNP levels 4. Proportion of participants who improve in WHO FC 5. Time to death or the first occurrence of any of the following clinical worsening events (TTCW) • Worsening-related listing for lung and/or heart transplant • Need to initiate rescue therapy with an approved background PAH therapy or the need to increase the dose of infusion prostacyclin by 10% or more • Need for atrial septostomy • Hospitalization for worsening of PAH (= 24 hours) • Deterioration of PAH, defined by both of the following events occurring at any time, even if they began at different times, as compared to their baseline values: - Worsened WHO FC - Decrease in 6MWD by = 15% confirmed by 2 tests at least 4 hours apart, but no more than 1 week 6. Proportion of participants who maintain or achieve a low risk score using the simplified French Risk score calculator 7. Change from baseline in EuroQoL - 5 dimensions (EQ-5D-5L) index score 8. Change from baseline in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT®);Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Ireland, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Serbia, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactSaraBeth Hahn
Acceleron Pharma Inc.
Outcome results
None listed