Clinical trial NCT04766892: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Keywords: HFpEF
NT-proBNP
Cardiac troponin T
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Number of Participants With Cardiac Rhythm Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Ratio to Baseline at Week 26 in Resting N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels
timeFrame: At Week 26
measure: Ratio to Baseline at Week 26 in Resting High Sensitivity Cardiac Troponin T (Hs-cTnT) Levels Assessed by High-Sensitivity Assay
timeFrame: At Week 26
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0028
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 0019
state: Arizona
city: Tucson
country: United States
facility: Local Institution - 0011
state: Arizona
city: Los Angeles
country: United States
facility: Local Institution - 0005
state: California
city: San Francisco
country: United States
facility: Local Institution - 0026
state: California
city: Jacksonville
country: United States
facility: Local Institution - 0020
state: Florida
city: Miami
country: United States
facility: Local Institution - 0014
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0018
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0004
state: Illinois
city: Hazel Crest
country: United States
facility: Local Institution - 0023
state: Illinois
city: Slidell
country: United States
facility: Local Institution - 0017
state: Louisiana
city: Grand Rapids
country: United States
facility: Local Institution - 0007
state: Michigan
city: New York
country: United States
facility: Local Institution - 0012
state: New York
city: Durham
country: United States
facility: Local Institution - 0003
state: North Carolina
city: Oklahoma City
country: United States
facility: Local Institution - 0016
state: Oklahoma
city: Portland
country: United States
facility: Local Institution - 0010
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0001
state: Oregon
city: Philadelphia
country: United States
facility: Local Institution - 0002
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0008
state: South Carolina
city: Salt Lake City
country: United States
facility: Local Institution - 0006
state: Utah
city: Toronto
country: Canada
facility: Local Institution - 0034
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: