Mavacamten in Heart Failure With HFpEF and Chronic Elevation of Cardiac Biomarkers

What is the Purpose of this Study?

This study focuses on individuals who have a condition called HFpEF (heart failure with preserved ejection fraction). HFpEF occurs when the lower left chamber (left ventricle) is not able to fill properly with blood during the diastolic (filling) phase. The study will evaluate whether an investigational drug called mavacamten can lower blood levels of cardiac troponin (a marker of heart muscle injury) and/or NT-proBNP (a marker of heart wall stress), referred to as “cardiac biomarkers.” These cardiac biomarkers are increased in the blood of some people with heart failure with preserved ejection fraction (HFpEF). Additionally, the study will provide preliminary information regarding the tolerability and safety of mavacamten treatment in HFpEF. Given the open label design of the study, all enrolled patients will receive the study medication.

Eligibility

Is at least 50 years old at Screening.
Body weight is greater than 45 kg at Screening.
Documented prior objective evidence of heart failure as shown by 1 or more of the following criteria:

Key Inclusion Criteria:

Is at least 50 years old at Screening.
Body weight is greater than 45 kg at Screening.
Documented prior objective evidence of heart failure as shown by 1 or more of the following criteria:
Previous hospitalization for heart failure with documented radiographic evidence of pulmonary congestion.
Elevated LV end-diastolic pressure or pulmonary capillary wedge pressure at rest (≥15 mm Hg) or with exercise (≥25 mm Hg).
Elevated level of NT-proBNP (>400 pg/mL) or brain natriuretic peptide (BNP) (>200 pg/mL).
Echocardiographic evidence of medial E/e' ratio ≥ 15 or left atrial enlargement (left atrial volume index >34 mL/m2) together with chronic treatment with spironolactone, eplerenone, or a loop diuretic.
Meets 1 or more of the following criteria:
A screening hs-cTnT ≥ 99th percentile AND a screening NT-proBNP > 200 pg/mL (if not in atrial fibrillation or atrial flutter) or > 500 pg/mL (if in atrial fibrillation or atrial flutter) OR if the screened participant is of African descent or has a body mass index (BMI) ≥ 30.0 kg/m2, a screening hs-cTnT ≥ 99th percentile, AND a screening NT-proBNP > 160 pg/mL (if not in atrial fibrillation or atrial flutter) or > 400 pg/mL (if in atrial fibrillation or atrial flutter).
A screening NT-proBNP > 300 pg/mL (if not in atrial fibrillation or atrial flutter) or > 750 pg/mL (if in atrial fibrillation or atrial flutter) OR if the screened participant is of African descent or has a BMI ≥ 30.0 kg/m2, a screening NT-proBNP > 240 pg/mL (if not in atrial fibrillation or atrial flutter) or > 600 pg/mL (if in atrial fibrillation or atrial flutter).
Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.
Has maximal left ventricular wall thickness ≥12 mm OR documented elevated left ventricular mass index by 2-dimensional imaging (>95 g/m2 if female and >115 g/m2 if male).
Has high quality TTEs without or with echocardiographic contrast agents.
Has NYHA class II or III symptoms at Screening.

Key Exclusion Criteria:

Has a prior diagnosis of HCM OR a known infiltrative or storage disorder causing HFpEF and/or cardiac hypertrophy, such as amyloidosis, Fabry disease, or Noonan syndrome with LV hypertrophy OR a positive serum immunofixation result.
Has a history of syncope within the last 6 months or sustained ventricular tachycardia with exercise within the past 6 months.
Has a history of resuscitated sudden cardiac arrest at any time or known appropriate implantable cardioverter defibrillator discharge within 6 months prior to Screening.
Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or is not adequately rate controlled within 6 months prior to Screening.
Currently treated or planned treatment during the study with either: (a) a combination of beta blocker and verapamil or a combination of beta blocker and diltiazem, (b) disopyramide, or (c) biotin or biotin-containing supplements/multivitamins.
Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral stenosis, or severe mitral or tricuspid regurgitation at Screening.
Has severe chronic obstructive pulmonary disease, or other severe pulmonary disease, requiring home oxygen, chronic nebulizer therapy, chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months.
Has body mass index ≥45.0 kg/m2.
Has left ventricular global longitudinal strain by TTE in the range from 0 to -12.0 (assessed by the central laboratory).
Has NT-proBNP at Screening >2000 pg/mL.
Has acute decompensated heart failure events requiring intravenous (IV) diuretics, IV inotropes, IV vasodilators, or a left ventricular assist device within 30 days prior to Screening.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

AN EXPLORATORY, OPEN-LABEL, PROOF-OF-CONCEPT, PHASE 2A STUDY OF MAVACAMTEN IN PARTICIPANTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION AND CHRONIC ELEVATION OF CARDIAC TROPONIN I AND/OR NT-PROBNP

Study Details

Disease Type/Condition

Other

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

IRB Number

STUDY00001276

ClinicalTrials.gov ID

NCT04766892

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org