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

NCT04766892 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CV027-005
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 21

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

Keywords

HFpEF; NT-proBNP; Cardiac troponin T

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (1)

mavacamten (MYK-461)

EXPERIMENTAL

Drug: mavacamten

Interventions

mavacamten DRUG

mavacamten capsules

mavacamten (MYK-461)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is at least 50 years old at Screening.
• Body weight is greater than 45 kg at Screening.
• 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.
• Meets 1 or more of the following criteria:
• 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).
• 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).
• Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.
• 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).
• Has high quality TTEs without or with echocardiographic contrast agents.
• Has NYHA class II or III symptoms at Screening.

You may not qualify if:

• 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.
• Has a history of syncope within the last 6 months or sustained ventricular tachycardia with exercise within the past 6 months.
• Has a history of resuscitated sudden cardiac arrest at any time or known appropriate implantable cardioverter defibrillator discharge within 6 months prior to Screening.
• 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.
• 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.
• Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral stenosis, or severe mitral or tricuspid regurgitation at Screening.
• 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.
• Has body mass index ≥45.0 kg/m2.
• Has left ventricular global longitudinal strain by TTE in the range from 0 to -12.0 (assessed by the central laboratory).
• Has NT-proBNP at Screening \>2000 pg/mL.
• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Local Institution - 0028

Birmingham, Alabama, 35249, United States

Location

Local Institution - 0019

Phoenix, Arizona, 85016, United States

Location

Local Institution - 0011

Tucson, Arizona, 85724, United States

Location

Local Institution - 0005

Los Angeles, California, 90027, United States

Location

Local Institution - 0026

San Francisco, California, 94158, United States

Location

Local Institution - 0020

Jacksonville, Florida, 32216, United States

Location

Local Institution - 0014

Miami, Florida, 33133, United States

Location

Local Institution - 0018

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0004

Chicago, Illinois, 60611, United States

Location

Local Institution - 0023

Hazel Crest, Illinois, 60429, United States

Location

Local Institution - 0017

Slidell, Louisiana, 70458, United States

Location

Local Institution - 0007

Grand Rapids, Michigan, 49503, United States

Location

Local Institution - 0012

New York, New York, 10065, United States

Location

Local Institution - 0003

Durham, North Carolina, 27710, United States

Location

Local Institution - 0016

Oklahoma City, Oklahoma, 73135, United States

Location

Local Institution - 0010

Portland, Oregon, 97225, United States

Location

Local Institution - 0001

Portland, Oregon, 97239, United States

Location

Local Institution - 0002

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0008

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0006

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 0034

Toronto, Ontario, M5S 1B2, Canada

Location

Related Publications (1)

• 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.

  PMID: 39347697 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Cardiomyopathy, Familial Restrictive, 3

Interventions

MYK-461

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 23, 2021
• Study Start: March 30, 2021
• Primary Completion: February 26, 2024
• Study Completion: February 26, 2024
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-03

Locations

CA (1); US (20)