A Phase 2, Double-blind, Randomized, Placebocontrolled Study to Evaluate the Effects of Sotatercept versus Placebo for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection Fraction (HFpEF)
R
Roberto Machado, MD
Primary Investigator
Enrolling By Invitation
18-85 years
All
Phase
2
2 Locations
Brief description of study
This study is designed to evaluate the efficacy, measured by change from baseline in PVR (primary endpoint) and 6MWD (key secondary endpoint) of sotatercept versus placebo in adults with Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection Fraction (HFpEF).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: heart failure,pulmonary hypertension
-
Age: Between 18 Years - 85 Years
-
Gender: All
Inclusion Criteria:
- Age 18 to 85 years
- Clinical diagnosis of HFpEF:
- Left ventricular ejection fraction ≥ 50%, with no history of LVEF below 45
3. Demonstrated Cpc-PH by all of the following
- Baseline RHC performed within 10 days prior to Visit 1(during the Screening Period) documenting a minimum PVR of ≥ 320 dyn•sec/cm5 (4 wood units)
- Mean pulmonary arterial pressure (mPAP) of > 20 mmHg
- Pulmonary capillary wedge pressure (PCWP) > 15 mmHg but < 30 mmHg
4. New York Heart Association FC of II or III
5. Six-Minute Walk Distance ≥ 100 m repeated twice during screening and both values within 15% of each other, calculated
from the highest value.
6. Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for ≥ 30 days
prior to Visit 1. Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within
30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1. Anticoagulation may be
suspended for RHC if necessary.
7. Women of childbearing potential (defined in Appendix 2) must:
- Have a negative pregnancy test as verified by the investigator prior to starting study drug administration; shemust 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 continue 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 drug
- 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 drug
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 (see Appendix 2 for additional contraceptive information)
- Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study
drug.
9. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements.
10. Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
11. Ability to understand and provide written informed consent for participation
Exclusion Criteria:
1. A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
2. Significant parenchymal lung disease (e.g., chronic obstructive pulmonary disease with Global Initiative for Obstructive Lung
Disease (GOLD) criteria III and IV, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis,
pulmonary thromboembolism)
3. Cardiovascular co-morbidities, which include any of the following:
-
Any history of greater than mild mitral regurgitation or aorticregurgitation valvular disease or greater than mild aortic or mitral stenosis.
- Acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1.
- Uncontrolled heart rate (> 100 bpm) from atrial fibrillation or atrial flutter
- History of serious life-threatening or hemodynamically significant arrhythmia
- History of or anticipated heart transplant or ventricular assist device implantation
- History of or anticipated implantation of pacemaker or implantable cardioverter defibrillator
- Occurrence of myocardial infarction within 90 days of Visit 1.
- History of known pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy
- Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 110 mmHg during Screening after a period of rest
- Systemic hypotension as evidenced by sitting systolic blood pressure < 90 mmHg or sitting diastolic blood pressure < 50 mmHg during Screening
- Resting heart rate of < 45 bpm or > 115 bpm
- Cerebrovascular accident within 90 days of Visit 1
- Acutely decompensated HF within 45 days prior to Visit 1, as per investigator assessment
- Electrocardiogram (ECG) during Screening Period with Fridericia’s corrected QT interval (QTcF) > 480 msec or > 500 msec if a ventricular conduction defect (right bundle branch block; left bundle branch block; or interventricular conduction delay) is present
- Personal or family history of long corrected QT syndrome or sudden cardiac death in first-degree relative
4. Hospitalization for any indication within 30 days of Visit 1
5. Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5
inhibitors, or soluble guanylate cyclase stimulators) within 30 days prior to Visit 1
6. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to Visit 1
7. Received erythropoietin within 6 months prior to Visit 1
8. Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection
and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A through C)
9. Prior exposure to sotatercept or luspatercept
10. Currently enrolled in or have completed any other investigational product study within 30 days for small-molecule
drugs or within 5 half-lives for biologics prior to the date of signed informed consent
11. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Visit 1 or planned initiation
during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the
study are eligible)
12. Any of the following clinical laboratory values prior to Visit 1 as specified:
o Hemoglobin (Hgb) above the gender-specific upper limit of normal (ULN) per local laboratory test within 28 days
of Visit 1or < 10 g/dL per local laboratory within 28 days of Visit 1
o Serum alanine aminotransferase or aspartate aminotransferase levels > 3× ULN or total bilirubin
> 1.5× ULN within 28 days of Visit 1
o Estimated glomerular filtration rate < 30 ml/min/1.73 m2 (4-variable Modification of Diet in Renal Disease
equation) within 28 days of Visit 1 or required renal replacement therapy within 90 days of Visit 1
o Glycated hemoglobin (HbA1c) > 10% within 28 days of Visit 1
o Platelet count < 75,000/mm3 within 28 days of Visit 1
13. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the
investigational product
14. Major surgery within 60 days prior to Visit 1. Participants must have completely recovered from any previous surgery prior to
Visit 1
15. Prior heart-lung transplants or life expectancy of < 12 months
16. Pregnancy or breastfeeding in females
17. History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or ≤ 2
squamous cell carcinomas of the skin
18. History of clinically significant (as determined by the investigator) endocrine, hematologic, hepatic, (auto)immune,
metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may
limit participation in the study
19. Body mass index ≥ 45 kg/m2
Updated on
01 Aug 2024.
Study ID: 14340
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