Summary

Eligibility
for people ages 50 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

This is a Phase 2a proof-of-concept study to assess safety, tolerability, and preliminary efficacy of mavacamten treatment on biomarker levels in participants with heart failure with preserved ejection fraction (HFpEF) and elevation of NT-proBNP with or without elevation of cTnT. Data from this study will inform future study designs of mavacamten in patients with HFpEF.

Official Title

An Exploratory, Open-label, Proof-of-concept, Phase 2a Study of Mavacamten (MYK-461) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Chronic Elevation of Cardiac Biomarkers

Keywords

Heart Failure With Preserved Ejection Fraction, HFpEF, NT-proBNP, Cardiac troponin T, Heart Failure, mavacamten, mavacamten (MYK-461)

Eligibility

You can join if…

Open to people ages 50 years and up

  1. Is at least 50 years old at Screening.
  2. Body weight is greater than 45 kg at Screening.
  3. Documented prior objective evidence of heart failure as shown by 1 or more of the following criteria:
  4. Previous hospitalization for heart failure with documented radiographic evidence of pulmonary congestion.
  5. Elevated LV end-diastolic pressure or pulmonary capillary wedge pressure at rest (≥15 mm Hg) or with exercise (≥25 mm Hg).
  6. Elevated level of NT-proBNP (>400 pg/mL) or brain natriuretic peptide (BNP) (>200 pg/mL).
  7. 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.
  8. Meets 1 or more of the following criteria:
  9. 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).
  10. 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).
  11. Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.
  12. 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).
  13. Has high quality TTEs without or with echocardiographic contrast agents.
  14. Has NYHA class II or III symptoms at Screening.

You CAN'T join if...

  1. 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.
  2. Has a history of syncope within the last 6 months or sustained ventricular tachycardia with exercise within the past 6 months.
  3. Has a history of resuscitated sudden cardiac arrest at any time or known appropriate implantable cardioverter defibrillator discharge within 6 months prior to Screening.
  4. 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.
  5. 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.
  6. Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral stenosis, or severe mitral or tricuspid regurgitation at Screening.
  7. 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.
  8. Has body mass index ≥45.0 kg/m2.
  9. Has left ventricular global longitudinal strain by TTE in the range from 0 to -12.0 (assessed by the central laboratory).
  10. . Has NT-proBNP at Screening >2000 pg/mL.
  11. . 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.

Locations

  • University of California San Francisco (UCSF) accepting new patients
    San Francisco California 94158 United States
  • Cedars-Sinai Medical Center accepting new patients
    Los Angeles California 90027 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Bristol-Myers Squibb
Links
BMS Clinical Trial Information BMS Clinical Trial Patient Recruiting FDA Safety Alerts and Recalls Investigator Inquiry Form
ID
NCT04766892
Phase
Phase 2 Heart Failure Research Study
Study Type
Interventional
Participants
Expecting 35 study participants
Last Updated