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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— EMBARK-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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04766892
• Other study ID #: CV027-005
• Status: Completed
• Phase: Phase 2
• Start date: March 30, 2021
• Est. completion date: February 26, 2024

Study information

• Verified date: June 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 26, 2024
• Est. primary completion date: February 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• mavacamten
mavacamten capsules

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	Women's College Hospital	Toronto	Ontario
Canada	Ciusss McQ	Trsoi-Rivieres	Quebec
Ireland	St Michaels Hospital	Dublin
United States	Local Institution - 0018	Atlanta	Georgia
United States	Local Institution - 0024	Aurora	Colorado
United States	Local Institution - 0028	Birmingham	Alabama
United States	Local Institution - 0008	Charleston	South Carolina
United States	Local Institution - 0004	Chicago	Illinois
United States	Local Institution - 0022	Chicago	Illinois
United States	Local Institution - 0015	Cincinnati	Ohio
United States	Local Institution - 0003	Durham	North Carolina
United States	Local Institution - 0013	Germantown	Tennessee
United States	Local Institution - 0007	Grand Rapids	Michigan
United States	Local Institution - 0023	Hazel Crest	Illinois
United States	Local Institution - 0021	Indianapolis	Indiana
United States	Local Institution - 0025	Iowa City	Iowa
United States	Local Institution - 0020	Jacksonville	Florida
United States	Local Institution - 0009	La Jolla	California
United States	Local Institution - 0005	Los Angeles	California
United States	Local Institution - 0014	Miami	Florida
United States	Local Institution - 0012	New York	New York
United States	Local Institution - 0016	Oklahoma City	Oklahoma
United States	Local Institution - 0027	Orange	California
United States	Local Institution - 0002	Philadelphia	Pennsylvania
United States	Local Institution - 0019	Phoenix	Arizona
United States	Local Institution - 0001	Portland	Oregon
United States	Local Institution - 0010	Portland	Oregon
United States	Local Institution - 0006	Salt Lake City	Utah
United States	Local Institution - 0026	San Francisco	California
United States	Local Institution - 0017	Slidell	Louisiana
United States	Local Institution - 0011	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events.		26 weeks
Primary	Mavacamten effect on NT-proBNP levels (at rest)	Specifically, change from baseline to Week 26 in NT-proBNP (resting)	26 weeks
Primary	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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting