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

NCT ID: NCT04766892

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-30
• Study Completion Date: 2024-02-26

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mavacamten (MYK-461)

Group Type: EXPERIMENTAL

mavacamten

Intervention Type: DRUG

mavacamten capsules

Interventions

mavacamten

mavacamten capsules

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 0028

Birmingham, Alabama, United States

Local Institution - 0019

Phoenix, Arizona, United States

Local Institution - 0011

Tucson, Arizona, United States

Local Institution - 0005

Los Angeles, California, United States

Local Institution - 0026

San Francisco, California, United States

Local Institution - 0020

Jacksonville, Florida, United States

Local Institution - 0014

Miami, Florida, United States

Local Institution - 0018

Atlanta, Georgia, United States

Local Institution - 0004

Chicago, Illinois, United States

Local Institution - 0023

Hazel Crest, Illinois, United States

Local Institution - 0017

Slidell, Louisiana, United States

Local Institution - 0007

Grand Rapids, Michigan, United States

Local Institution - 0012

New York, New York, United States

Local Institution - 0003

Durham, North Carolina, United States

Local Institution - 0016

Oklahoma City, Oklahoma, United States

Local Institution - 0010

Portland, Oregon, United States

Local Institution - 0001

Portland, Oregon, United States

Local Institution - 0002

Philadelphia, Pennsylvania, United States

Local Institution - 0008

Charleston, South Carolina, United States

Local Institution - 0006

Salt Lake City, Utah, United States

Local Institution - 0034

Toronto, Ontario, Canada

Countries

United States; Canada

References

Shah SJ, Rigolli M, Javidialsaadi A, Patel RB, Khadra S, Goyal P, Little S, Wever-Pinzon O, Owens AT, Skali H, Arora P, Solomon SD. Cardiac Myosin Inhibition in Heart Failure With Normal and Supranormal Ejection Fraction: Primary Results of the EMBARK-HFpEF Trial. JAMA Cardiol. 2025 Feb 1;10(2):170-175. doi: 10.1001/jamacardio.2024.3810.

Reference Type: DERIVED

PMID: 39347697 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

CV027-005

Identifier Type: -

Identifier Source: org_study_id