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: Active, not recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: mavacamten

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Study Connect Contact Center http://www.bmsstudyconnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Toronto, Ontario, Canada, M5S 1B2
      • Women's College Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Institut de Cardiologie de Montreal
    • Trsoi-Rivieres, Quebec, Canada, G8Z 3R9
      • Ciusss McQ
• Ireland
  • Dublin, Ireland
    • St Michaels Hospital
• 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
    • La Jolla, California, United States, 92037
      • Local Institution - 0009
    • Los Angeles, California, United States, 90027
      • Local Institution - 0005
    • Orange, California, United States, 92868
      • Local Institution - 0027
    • San Francisco, California, United States, 94158
      • Local Institution - 0026
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0024
  • 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, 60637
      • Local Institution - 0022
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0004
    • Hazel Crest, Illinois, United States, 60429
      • Local Institution - 0023
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Local Institution - 0021
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Local Institution - 0025
  • 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
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Local Institution - 0015
  • 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
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0013
  • 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
Frequency and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events.		26 weeks
Mavacamten effect on NT-proBNP levels (at rest)	Specifically, change from baseline to Week 26 in NT-proBNP (resting)	26 weeks
Mavacamten effect on cTnT levels (at rest)	Specifically, change from baseline to Week 26 in cTnT (resting), as assessed by a high-sensitivity assay	26 weeks

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
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): April 15, 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): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: HFpEF; NT-proBNP; Cardiac troponin T
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular 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