Heart Failure With Preserved Ejection FractionPhase 2EMBARK-HFpEFNCT04766892
A Study of Mavacamten in Participants With HFpEF and Elevation of NT-proBNP With or Without Elevation of cTnT
A Phase 2 study testing mavacamten in people with Heart Failure With Preserved Ejection Fraction, run by Bristol-Myers Squibb at 21 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- mavacamten
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 30 Mar 2021to 26 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States20 sites
Local Institution - 0018
Atlanta, Georgia, 30322
Local Institution - 0028
Birmingham, Alabama, 35249
Local Institution - 0008
Charleston, South Carolina, 29425
Local Institution - 0004
Chicago, Illinois, 60611
Local Institution - 0003
Durham, North Carolina, 27710
Local Institution - 0007
Grand Rapids, Michigan, 49503
Local Institution - 0023
Hazel Crest, Illinois, 60429
Local Institution - 0020
Jacksonville, Florida, 32216
Local Institution - 0005
Los Angeles, California, 90027
Local Institution - 0014
Miami, Florida, 33133
Local Institution - 0012
New York, New York, 10065
Local Institution - 0016
Oklahoma City, Oklahoma, 73135
Local Institution - 0002
Philadelphia, Pennsylvania, 19104
Local Institution - 0019
Phoenix, Arizona, 85016
Local Institution - 0010
Portland, Oregon, 97225
Local Institution - 0001
Portland, Oregon, 97239
Local Institution - 0006
Salt Lake City, Utah, 84112
Local Institution - 0026
San Francisco, California, 94158
Local Institution - 0017
Slidell, Louisiana, 70458
Local Institution - 0011
Tucson, Arizona, 85724
About this study
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
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.
- Being tested
- mavacamten
- Keywords
- HFpEF, NT-proBNP, Cardiac troponin T
- Medical subject headings
- Cardiomyopathy, Familial Restrictive, 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mavacamtenDrug
mavacamten capsules
| Study group | Role | What they receive |
|---|---|---|
| mavacamten (MYK-461) | Experimental | Not described Receives: Drug: mavacamten |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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%
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2021
- Study start30 Mar 2021
- Primary completion26 Feb 2024
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04766892
- Sponsor's protocol ID
- CV027-005
- Acronym
- EMBARK-HFpEF
- Status last verified
- Mar 2025
- First submitted
- 16 Feb 2021
- Last updated
- 20 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 39347697
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04766892
- Acronym / sponsor ID
- EMBARK-HFpEF / CV027-005
- Keywords
- HFpEF, NT-proBNP, Cardiac troponin T
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 30 Mar 2021 (actual)
- Primary completion
- 26 Feb 2024 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 23 Feb 2021 (actual)
- Results
- Posted 20 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mavacamten (MYK-461) | Experimental | Drug: mavacamten |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- Meets 1 or more of the following criteria:
- Has documented LVEF ≥60% at the Screening visit and no history of prior LVEF ≤ 45%.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mavacamtenmavacamten capsules | Drug | mavacamten (MYK-461) |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: 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)
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.
Number of Participants With Adverse Events of Special Interest (AESIs)
Time frame: 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)
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%
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: 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)
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.
Number of Participants With Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Time frame: 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)
Blood samples were collected to assess the abnormalities in laboratory parameters.
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Time frame: 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)
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.
Number of Participants With Cardiac Rhythm Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Time frame: 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)
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.
Ratio to Baseline at Week 26 in Resting N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels
Time frame: At Week 26
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.
Ratio to Baseline at Week 26 in Resting High Sensitivity Cardiac Troponin T (Hs-cTnT) Levels Assessed by High-Sensitivity Assay
Time frame: At Week 26
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39347697Shah 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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mavacamten in people with Heart Failure With Preserved Ejection Fraction, run by Bristol-Myers Squibb at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: 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)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04766892, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.