Summary

Eligibility
for people ages 18-85 (full criteria)
Location
at Orange, California and other locations
Dates
study started
estimated completion

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, 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:

  1. Age 18 to 85 years
  2. Clinical diagnosis of HFpEF:

Left ventricular ejection fraction ≥50%, with no history of LVEF below 45% in more than two consecutive measurements

  1. Demonstrated Cpc-PH by all of the following:
  2. Baseline RHC performed within 28 days of or at Visit 1 (during the Screening Period) documenting a minimum PVR of ≥320 dyn•sec/cm5 (4 wood units)
  3. Mean pulmonary arterial pressure (mPAP) of >20 mmHg
  4. Pulmonary capillary wedge pressure (PCWP) >15 mmHg but < 30 mmHg
  5. New York Heart Association FC of II or III
  6. Six-minute Walk Distance ≥100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value
  7. 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.
  8. Women of childbearing potential must:
  9. Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
  10. 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 drug
  11. 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
  12. Male participants must:
  13. 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
  14. 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
  15. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
  16. . Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
  17. . 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:

  1. A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
  2. Documented significant lung disease:
  3. Chronic obstructive pulmonary disease with post-bronchodilator forced expiratory volume in the first second (FEV1) <60% predicted
  4. Restrictive lung disease with total lung capacity <70% predicted
  5. 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)
  6. Cardiovascular co-morbidities, which include any of the following:
  7. Any history of greater than mild mitral or aortic regurgitation valvular disease or greater than mild aortic or mitral stenosis. Severe tricuspid regurgitation may be included unless it is due to primary valvular disease, e.g., from endocarditis, carcinoid, or mechanical destruction
  8. Acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1
  9. Uncontrolled heart rate (> 100 bpm) from atrial fibrillation or atrial flutter
  10. History of serious life-threatening or hemodynamically significant arrhythmia
  11. History of or anticipated heart transplant or ventricular assist device implantation
  12. Anticipated implantation of pacemaker, pacemaker implantation within 30 days of Screening or history of implantable cardioverter defibrillator placement
  13. Occurrence of myocardial infarction within 180 days of Visit 1
  14. History of known pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy
  15. 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
  16. Systemic hypotension as evidenced by sitting systolic blood pressure <90 mmHg or sitting diastolic blood pressure <50 mmHg during Screening
  17. Resting heart rate of <45 bpm or >115 bpm
  18. Stroke within 90 days of Visit 1
  19. Acutely decompensated HF that required hospitalization within 30 days of Visit 1
  20. 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
  21. Personal or family history of Brugada syndrome
  22. Personal or family history of long QT syndrome unless the participant's ECG shows a normal QTc
  23. Arrhythmogenic right ventricular dysplasia (ARVD) unless the participant has a recent cardiac MRI that shows no evidence of this diagnosis
  24. Personal history of sudden cardiac arrest or family history of unexplained sudden cardiac death or arrest
  25. History of or anticipated cardiac valve replacement or repair (mechanical or biomechanical)
  26. Hospitalization for any indication within 30 days of Visit 1
  27. 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
  28. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days of Visit 1
  29. Received erythropoietin within 6 months of Visit 1
  30. 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)
  31. Prior exposure to sotatercept or luspatercept
  32. . 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
  33. . 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)
  34. . Any of the following clinical laboratory values prior to Visit 1 as specified:
  35. 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
  36. Serum alanine aminotransferase or aspartate aminotransferase levels >3× ULN or total bilirubin >3× ULN within 28 days of Visit 1
  37. 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
  38. Glycated hemoglobin (HbA1c) >10% within 28 days of Visit 1
  39. Platelet count < 75,000/mm3 within 28 days of Visit 1
  40. . History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
  41. . Major surgery within 60 days of Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1
  42. . Prior heart-lung transplants or life expectancy of <12 months
  43. . Pregnancy or breastfeeding in females
  44. . 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
  45. . 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
  46. . Body mass index ≥50 kg/m2
  47. . Untreated or more than mild obstructive sleep apnea
  48. . 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 92868-2994 United States
  • Cedars Sinai Medical Center ( Site 1082) accepting new patients
    Los Angeles California 90048 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
ID
NCT04945460
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 150 study participants
Last Updated