Pulmonary Arterial Hypertension
Conditions
Interventions
Each eligible participant will be randomized in a 1:1 ratio to 1 of the
following 2 treatment arms during the DBPC Treatment Period:
• Arm 1: Placebo administered subcutaneously (SC) every 21 days pl
Sponsors
Acceleron, Pharma Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years 2. Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of >= 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of = 6 or COMPERA 2.0 risk score >= 2 (intermediate-low-risk or above) 5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening. Background PAH therapy and diuretics are further defined in Section 7.2. 6. 6MWD >= 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value) 7. Females of childbearing potential (as defined in Appendix 4) must meet the following criteria: • Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; • Agree to ongoing pregnancy testing (either urine or serum) during the course of the study and until 8 weeks after the last dose of the study drug • If sexually active with a male partner: - Used highly effective contraception without interruption for at least 28 days prior to starting the investigational product AND - Agreed to use the same highly effective contraception in combination with a barrier method 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 meet the following criteria: • Agree to use a condom, defined as a male latex condom or nonlatex 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 16 weeks (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 documented informed consent
Exclusion criteria
Exclusion criteria: 1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5 2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease and pulmonary capillary hemangiomatosis 3. Hgb at screening above gender-specific upper limit of normal (ULN), per local laboratory test 4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest 5. Baseline systolic BP 3 × ULN (For United Kingdom [UK], refer to the specific requirement in Appendix 6) • Platelet count 500 ms during the Screening Period (For UK and South Korea, refer to the specific requirements in Appendix 6). 19. Personal or family history of long QT syndrome or sudden cardiac death 20. Left ventricular ejection fraction = 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is TTCW, defined as the time from randomization to the first confirmed morbidity event or death. The events that will comprise this endpoint include the following: • All-cause death • Non-planned PAH-related hospitalization of >= 24 hours in duration • Atrial septostomy • Lung transplant • Deterioration in performance in exercise testing due to PAH, defined as a decrease in 6MWD from baseline (average of screening) on 2 consecutive tests (which must be at least 4 hours apart) and at least 1 of the following: - Worsening of WHO FC from baseline - Signs/symptoms of increased right heart failure - Addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral All events will be adjudicated by a blinded, independent committee of clinical experts. | — |
Secondary
| Measure | Time frame |
|---|---|
| The 9 secondary endpoints are ranked as follows: 1. Multicomponent improvement endpoint measured by the proportion of participants achieving all of the following at Week 24 relative to baseline: • Improvement in 6MWD (increase >= 30 meters [m]) • Improvement in NT-proBNP (decrease in NT-proBNP >= 30%) or maintenance/achievement of NT-proBNP level | — |
Countries
Netherlands
Outcome results
None listed