A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified April 2025 by Bristol-Myers Squibb
Sponsor
Bristol-Myers Squibb
Information Provided by (Responsible Party)
Bristol-Myers Squibb
Clinicaltrials.gov Identifier
NCT04349072
Other Study ID Numbers:
CV027-006
First Submitted
April 6, 2020
First Posted
April 15, 2020
Results First Posted
February 6, 2023
Last Update Posted
May 22, 2025
Last Verified
April 2025

ClinicalTrials.gov processed this data on May 2025Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
HOCM, Hypertrophic Obstructive Cardiomyopathy
Drug: MavacamtenDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment112 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Randomized, Double-blind, Placebo-controlled Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy
Study Start DateJuly 5, 2020
Actual Primary Completion DateFebruary 6, 2022
Actual Study Completion DateMay 19, 2024

Groups and Cohorts

Group/CohortIntervention/Treatment
Drug: Mavacamten
Mavacamten Capsules Other names: MYK-461
Drug: Mavacamten
Mavacamten Capsules Other names: MYK-461
Drug: Placebo
Matching Placebo Capsules
Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures
  1. Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16
    Participants who decided to proceed with SRT or were eligible for SRT at week 16. Participants with missing assessments were classified as meeting the primary endpoint (did not improve). SRT eligibility using the New York Heart Association Functional Class (NYHA) and left ventricular outflow tract (LVOT) assessments per the 2011 ACCF/AHA guideline clinical and hemodynamic criterion are below: * NYHA Class III or IV/ NYHA Class II with exertion-induced syncope/near syncope, AND * Dynamic LVOT gradient at rest or with provocation \>= 50 mmHg. NYHA Class II at week 16, the following rules will be applied: * NYHA Class II with history of exertional syncope/ syncope at baseline and at W16 is still NYHA Class II, they remain SRT eligible IF their maximal LVOT gradient is ≥ 50mmHg * NYHA Class III/IV at baseline and at W16 has improved to Class II, they are no longer SRT eligible UNLESS they have AE of exertional syncope or pre-syncope during the 16 weeks.
Secondary Outcome Measures
  1. Number of Participants With at Least One Class Improvement From Baseline in New York Heart Association (NYHA) Class at Week 16
    The NYHA functional classification of heart failure assigns participants to 1 of 4 categories based on the participants symptoms. Baseline values are defined generally as the last available value before the first administration of study drug of analysis interest. Participants with missing NYHA class assessments are treated as no improvement. Class 1: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). Class 2: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class 3: Marked limitation of physical activity. Comfortable at rest. Less-than ordinary-activity causes fatigue, palpitation, or dyspnea. Class 4: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
  2. Change From Baseline to Week 16 in Kansas City Cardiomyopathy Questionnaire 23-item Version, Clinical Summary Score (KCCQ-23, CSS)
    The KCCQ-23 is a 23-item, self-administered questionnaire that measures the impact of a participant's cardiovascular disease or its treatment on 6 distinct domains using a 2-week recall period: symptoms/signs, physical limitation, quality of life (QoL), social limitations, self-efficacy, and symptom stability. The KCCQ 23 Clinical Summary Score (CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ 23. The CSS, TSS, and the PL score range from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations. The CSS is a mean of the TSS and the PL score.
  3. Change From Baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP)
    A geometric mean ratio was used to assess the change from baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP). Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.
  4. Change From Baseline to Week 16 in Cardiac Troponin
    A geometric mean ratio was used to assess the change from baseline to week 16 in cardiac troponin. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.
  5. Change From Baseline to Week 16 in Post-Exercise Left Ventricular Outflow Tract (LVOT) Gradient
    Change from baseline to week 16 in post-exercise left ventricular outflow tract (LVOT) gradient. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
At least 18 years old at screening and body weight \> 45 kg at screening
Diagnosed with oHCM consistent with current ACCF/AHA 2011 and meet their recommendations for invasive therapies
Referred or under active consideration within the past 12 months for SRT procedure and willing to have SRT procedure
Has documented left ventricular ejection fraction (LVEF) ≥ 60% at Screening
Has documented oxygen saturation at rest ≥ 90% at Screening Key
Exclusion Criteria
Persistent or permanent atrial fibrillation and subject not on anticoagulation for ≥ 4 weeks prior to screening and/or not adequately rate controlled ≤ 6 months prior to screening
Previously treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\])
For individuals on beta blockers, calcium channel blockers, or disopyramide, any dose adjustment of these medications \< 14 days prior to screening or an anticipated change in regimen during the first 16 weeks of the study
Any medical condition that precludes upright exercise stress testing
Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at screening
Prior treatment with cardiotoxic agents, such as doxorubicin or similar
Has a history or evidence of any other clinically significant disorder, condition, or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

Contacts and Locations

Sponsors and CollaboratorsBristol-Myers Squibb
Locations
Local Institution - 0009 | Los Angeles California, United States, 90027Local Institution - 0011 | Stanford California, United States, 94305 5406Local Institution - 0001 | New Haven Connecticut, United States, 06520Local Institution - 0021 | Weston Florida, United States, 33331Local Institution - 0016 | Boston Massachusetts, United States, 02114-2696Local Institution - 0007 | Boston Massachusetts, United States, 02115Local Institution - 0006 | Ann Arbor Michigan, United States, 48109Local Institution - 0013 | Grand Rapids Michigan, United States, 49503Local Institution - 0015 | Rochester Minnesota, United States, 55905Local Institution - 0005 | St Louis Missouri, United States, 63110Local Institution - 0010 | New York New York, United States, 10016Local Institution - 0017 | Valhalla New York, United States, 10595Local Institution - 0004 | Durham North Carolina, United States, 27710Local Institution - 0020 | Cleveland Ohio, United States, 44195Local Institution - 0002 | Portland Oregon, United States, 97239Local Institution - 0003 | Philadelphia Pennsylvania, United States, 19104Local Institution - 0019 | Pittsburgh Pennsylvania, United States, 15212Local Institution - 0014 | Nashville Tennessee, United States, 37205Local Institution - 0018 | Nashville Tennessee, United States, 37235Local Institution | Houston Texas, United States, 77030Local Institution - 0012 | Murray Utah, United States, 84107-5701
Investigators
Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full Text)
Documents provided by Bristol-Myers SquibbStudy Protocol and Statistical Analysis Plan  June 29, 2022