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

• ClinicalTrials.gov Identifier: NCT04766892
• Recruitment Status: Recruiting
• First Posted: February 23, 2021
• Last Update Posted: June 14, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: February 16, 2021
• First Posted Date: February 23, 2021
• Last Update Posted Date: June 14, 2022
• Actual Study Start Date: March 30, 2021
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 26, 2022)

• Frequency and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events. [ Time Frame: 26 weeks ]
• Mavacamten effect on NT-proBNP levels (at rest) [ Time Frame: 26 weeks ]
  Specifically, change from baseline to Week 26 in NT-proBNP (resting)
• Mavacamten effect on cTnT levels (at rest) [ Time Frame: 26 weeks ]
  Specifically, change from baseline to Week 26 in cTnT (resting), as assessed by a high-sensitivity assay

Original Primary Outcome Measures (submitted: February 19, 2021)

• Frequency and severity of treatment-emergent adverse events, adverse events of special interest, and serious adverse events. [ Time Frame: 26 weeks ]
• Mavacamten effect on cTnI levels (at rest) [ Time Frame: 26 weeks ]
  Specifically, change from baseline to Week 26 in cTnI (resting), as assessed by a high-sensitivity assay
• Mavacamten effect on NT-proBNP levels (at rest) [ Time Frame: 26 weeks ]
  Specifically, change from baseline to Week 26 in NT-proBNP (resting)

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Mavacamten in Participants With HFpEF and Elevation of NT-proBNP With or Without Elevation of cTnT
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Heart Failure With Preserved Ejection Fraction

Intervention

Drug: mavacamten

mavacamten capsules

Study Arms

Experimental: mavacamten (MYK-461)

Intervention: Drug: mavacamten

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 19, 2021): 35
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2023
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BMS Study Connect Contact Center http://www.bmsstudyconnect.com; 855-907-3286; clinical.trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04766892
• Other Study ID Numbers: CV027-005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: MyoKardia, Inc.
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: MyoKardia, Inc.
• Collaborators: Not Provided

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: June 2022