A Study of Sotatercept for the Treatment of Cpc-PH Due to HFpEF (MK-7962-007/A011-16)
a study on High Blood Pressure Pulmonary Hypertension Heart Failure
Summary
- Eligibility
- for people ages 18-85 (full criteria)
- Location
- at UC Irvine UCLA
- Dates
- study startedcompletion around
Description
Summary
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).
Official Title
A Phase 2, Double-blind, Randomized, Placebo-controlled 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)
Details
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.
Keywords
Hypertension, Pulmonary, Pulmonary, hypertension, Cpc PH, HFpEF, sotatercept, Pulmonary Hypertension, Hypertension, Sotatercept 0.3 mg/kg, Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg, Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg
Eligibility
You can join if…
Open to people ages 18-85
Participants must meet the following criteria to be enrolled in this proof-of-concept study:
- Age 18 to 85 years
Clinical diagnosis of HFpEF:
• Left ventricular ejection fraction ≥50%, with no history of LVEF below 45% in more than two consecutive measurements under stable conditions
- Demonstrated Cpc-PH by all of the following:
- Baseline RHC performed within 28 days of randomization 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
- New York Heart Association FC of II or III
- Six-minute Walk Distance ≥100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value
- 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.
- Women of childbearing potential must:
- Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; 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 with a male partner: use highly effective contraception without interruption for at least 28 days prior to starting the investigational product AND agree 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 drug
- 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 16 weeks (112 days) after the last dose of study drug
- Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
- Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
- Ability to understand and provide documented consent for participation
You CAN'T join if...
Participants will be excluded from the study if any of the following criteria are met:
- A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
- Documented significant lung disease:
- Chronic obstructive pulmonary disease with post-bronchodilator forced expiratory volume in the first second (FEV1) <60% predicted
- Restrictive lung disease with total lung capacity <70% predicted
- More than mild interstitial lung disease (ILD), with FVC<70% or FEV1<60% predicted (still appropriate if absence of more than mild ILD, fibrosis, or COPD on computed tomography [CT] imaging)
- Cardiovascular co-morbidities, which include any of the following:
- History of more than mild mitral or aortic stenosis
- Ongoing more than mild mitral or aortic regurgitation
- More than one valve replacement or repair (mechanical or biomechanical) or anticipation of any valve replacement or repair
- Severe tricuspid regurgitation due to primary valvular disease
- Occurrence of myocardial infarction, acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1
- History of serious life-threatening or hemodynamically significant arrhythmia
- History of or anticipated heart transplant or ventricular assist device implantation
- History of implantable cardioverter defibrillator placement or anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening
- Anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening or history of implantable cardioverter defibrillator placement
- Occurrence of myocardial infarction within 180 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
- Stroke within 90 days of Visit 1
- Acutely decompensated HF that required hospitalization within 30 days of Visit 1
- Electrocardiogram during Screening Period with Fridericia's corrected QT interval (QTcF) >470 msec for males or >480 msec for females, 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 Brugada syndrome, sudden cardiac arrest or unexplained sudden cardiac death or arrest
- Personal or family history of long QT syndrome unless the participant's ECG shows a normal QTc
- Arrhythmogenic right ventricular dysplasia (ARVD) unless the participant has a recent cardiac MRI that shows no evidence of this diagnosis
- Hospitalization for any worsening of medical conditions or any significant surgery per investigator within 30 days of Visit 1
- Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators) within 30 days of Visit 1
- Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin,or levosimendan) within 30 days of Visit 1
- Received erythropoietin within 6 months of Visit 1.The use of an oral phosphodiesterase type 5 inhibitor, if only indicated for erectile dysfunction, is permitted, if not administered within 48 hours of a study visit or procedure.
- Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), with severe hepatic impairment and/or cirrhosis (e.g., hepatic encephalopathy)
- Prior exposure to sotatercept or luspatercept
- Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented consent
- Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days of 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)
- Any of the following clinical laboratory values prior to Visit 1 as specified:
- 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
- Serum alanine aminotransferase or aspartate aminotransferase levels >3× ULN or total bilirubin >3× ULN within 28 days of Visit 1
- 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
- Glycated hemoglobin (HbA1c) >10% within 28 days of Visit 1
- Platelet count < 75,000/mm3 within 28 days of Visit 1
- History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
- Major surgery within 60 days of Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1
- Prior heart-lung transplants or life expectancy of <12 months
- Pregnancy or breastfeeding in females
- 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
- History of clinically significant (as determined by the investigator) endocrine, hematologic, hepatic, (auto)immune, infectious (requiring chronic antibiotics), metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study
- Body mass index ≥50 kg/m2
- Untreated or more than mild obstructive sleep apnea
- Any non-cardiopulmonary condition or acute/chronic impairment(s) (other than dyspnea) that limits the ability to perform 6-minute walk test (6MWT)
Locations
- University of California Irvine ( Site 1086)
accepting new patients
Orange California 92868 United States - Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 1028)
accepting new patients
Torrance California 90502 United States - Cedars Sinai Medical Center ( Site 1082)
accepting new patients
Los Angeles California 90048 United States - Stanford University ( Site 1024)
in progress, not accepting new patients
Stanford California 94305 United States
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Links
- Merck Clinical Trials Information
- ID
- NCT04945460
- Phase
- Phase 2 research study
- Study Type
- Interventional
- Participants
- Expecting 150 study participants
- Last Updated