A Study of Mavacamten in Participants With HFpEF and Elevation of NT-proBNP With or Without Elevation of cTnT (EMBARK-HFpEF)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: mavacamten

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 1B2
      • Local Institution - 0034
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Local Institution - 0028
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 0019
    • Tucson, Arizona, United States, 85724
      • Local Institution - 0011
  • California
    • Los Angeles, California, United States, 90027
      • Local Institution - 0005
    • San Francisco, California, United States, 94158
      • Local Institution - 0026
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Local Institution - 0020
    • Miami, Florida, United States, 33133
      • Local Institution - 0014
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0018
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0004
    • Hazel Crest, Illinois, United States, 60429
      • Local Institution - 0023
  • Louisiana
    • Slidell, Louisiana, United States, 70458
      • Local Institution - 0017
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Local Institution - 0007
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0012
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0003
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73135
      • Local Institution - 0016
  • Oregon
    • Portland, Oregon, United States, 97225
      • Local Institution - 0010
    • Portland, Oregon, United States, 97239
      • Local Institution - 0001
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0002
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0008
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Local Institution - 0006

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

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:

   • 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.

4. Meets 1 or more of the following criteria:

   1. 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).
   2. 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).
5. Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.
6. 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).
7. Has high quality TTEs without or with echocardiographic contrast agents.
8. Has NYHA class II or III symptoms at Screening.

Key Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mavacamten (MYK-461)	Drug: mavacamten; mavacamten capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent Adverse event (TEAE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Number of Participants With Adverse Events of Special Interest (AESIs)	Adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. AEs of special interest include: Symptomatic overdose, teratogenicity, and LVEF ≤30%	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)	Treatment-emergent serious adverse event (TESAE) is defined as any untoward medical occurrence at any dose that: Results in death, Is immediately life-threatening (places the participant at immediate risk of death from the event as it occurred), Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, Results in a congenital abnormality or birth defect, Is an important medical event that may not result in death, be life-threatening, or require hospitalization, but may be considered an SAE when, based upon appropriate medical judgment, it may require medical or surgical intervention to prevent any of the outcomes listed above.	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Number of Participants With Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)	Blood samples were collected to assess the abnormalities in laboratory parameters.	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent Adverse event (TEAE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Number of Participants With Cardiac Rhythm Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent Adverse event (TEAE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.	From the first dose of study drug through 56 days following last dose of study drug (assessed for an average of 225 days up to a max of approximately 270 days)
Ratio to Baseline at Week 26 in Resting N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels	Ratio to baseline in N-terminal pro B-type natriuretic peptide levels. The baseline value is defined as the last available value before the first administration of study drug.	At Week 26
Ratio to Baseline at Week 26 in Resting High Sensitivity Cardiac Troponin T (Hs-cTnT) Levels Assessed by High-Sensitivity Assay	Ratio to Baseline in resting high sensitivity cardiac troponin T (hs-cTnT) levels. The baseline value is defined as the last available value before the first administration of study drug.	At Week 26

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): February 26, 2024

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HFpEF; NT-proBNP; Cardiac troponin T
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: CV027-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No