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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04766892
Collaborator
(none)
35
Enrollment
24
Locations
1
Arm
25
Anticipated Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
35 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 30, 2021
Anticipated Primary Completion Date :
Apr 30, 2023
Anticipated Study Completion Date :
Apr 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: mavacamten (MYK-461)

Drug: mavacamten
mavacamten capsules

Outcome Measures

Primary Outcome Measures

  1. Frequency and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events. [26 weeks]

  2. Mavacamten effect on NT-proBNP levels (at rest) [26 weeks]

    Specifically, change from baseline to Week 26 in NT-proBNP (resting)

  3. Mavacamten effect on cTnT levels (at rest) [26 weeks]

    Specifically, change from baseline to Week 26 in cTnT (resting), as assessed by a high-sensitivity assay

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. Meets 1 or more of the following criteria:

  2. 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).

  3. 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).

  4. Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.

  5. 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).

  6. Has high quality TTEs without or with echocardiographic contrast agents.

  7. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Center For Clinical Research Phoenix Arizona United States 85016
2 Southern Arizona Va Health Care System Tucson Arizona United States 85724
3 University Of California - San Diego Medical Center La Jolla California United States 92037
4 Cedars-Sinai Medical Center Los Angeles California United States 90027
5 Local Institution - 0029 Orange California United States 92868
6 Jacksonville Center For Clinical Research Jacksonville Florida United States 32216
7 Infinite Clinical Research Miami Florida United States 33133
8 Emory University School Of Medicine Atlanta Georgia United States 30322
9 Northwestern University Chicago Illinois United States 60611
10 Local Institution Chicago Illinois United States 60637
11 Chicago Medical Research Hazel Crest Illinois United States 60429
12 Indiana University School of Medicine-Indianapolis Indianapolis Indiana United States 46202
13 Louisiana Heart Center Slidell Louisiana United States 70458
14 Spectrum Health Hospitals Grand Rapids Michigan United States 49503
15 Weill Cornell Medical Center New York New York United States 10065
16 Duke University Medical Center Durham North Carolina United States 27710
17 The Christ Hospital Cincinnati Ohio United States 45219
18 South Oklahoma Heart Research Oklahoma City Oklahoma United States 73135
19 Providence St. Vincent Medical Center Portland Oregon United States 97225
20 Oregon Health & Science University Portland Oregon United States 97239
21 University of Pennsylvania Philadelphia Pennsylvania United States 19104
22 Medical University of South Carolina Charleston South Carolina United States 29425
23 Stern Cardiovascular Foundation Inc Germantown Tennessee United States 38138
24 University of Utah Salt Lake City Utah United States 84112

Sponsors and Collaborators

  • Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT04766892
Other Study ID Numbers:
  • CV027-005
First Posted:
Feb 23, 2021
Last Update Posted:
Jun 14, 2022
Last Verified:
Jun 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bristol-Myers Squibb
HFpEF
NT-proBNP
Cardiac troponin T
Additional relevant MeSH terms:
Heart Failure

Study Results

No Results Posted as of Jun 14, 2022