Hypertrophic Cardiomyopathy
Conditions
Keywords
Symptomatic, Obstructive, Left ventricular outflow tract gradient
Brief summary
This is a multicenter open-label study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM) who previously participated in study MYK-461-004 (PIONEER-HCM).
Interventions
DRUGmavacamten
mavacamten capsules
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Completed Study MYK-461-004. Prior participation in a non-interventional observational study is allowed. * Body weight \> 45 kg at Screening * Has safety laboratory parameters (chemistry and hematology) within normal limits Key
Exclusion criteria
* Has QTcF \> \> 500 ms or any other ECG abnormality considered by the investigator to pose a risk to subject safety (eg, second degree atrioventricular block type II) * Since enrollment into Study MYK-461-004, has developed obstructive coronary artery disease (\> 70% stenosis in one or more arteries) or known moderate or severe aortic valve stenosis * Since enrollment into Study MYK-461-004, has developed any acute or serious comorbid condition (eg, major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the opinion of the investigator or medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion * Since enrollment into Study MYK-461-004 has developed clinically significant malignant disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events | From first dose to end of treatment + 56 days (Approximately an average of 240 Weeks) | 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. An SAE 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 Who Had Cardiovascular Death | From first dose to end of study, (approximately 260 weeks) | Number of participants who had died due to cardiovascular reasons. |
| Number of Participants Who Experienced Sudden Death | From first dose to end of study, (approximately 260 weeks) | Number of participants who experienced sudden death |
| Number of Participants Who Were Hospitalized for Cardiovascular Reasons. | From first dose to end of study, (approximately 260 weeks) | Number of participants who were hospitalized for cardiovascular reasons. |
| Number of Participants With LVEF < 50% as Measured by Echocardiography. | From first dose to end of study, (approximately 260 weeks) | Number of participants with LVEF \< 50% as measured by echocardiography. |
| Number of Participants With Heart Failure Due to Systolic Dysfunction, Defined as Asymptomatic LVEF < 50% | From first dose to end of study, (approximately 260 weeks) | Number of participants with heart failure due to systolic dysfunction, defined as asymptomatic LVEF \< 50% |
| Number of Participants Who Were Experienced Myocardial Infarction | From first dose to end of study, (approximately 260 weeks) | Number of participants who experienced myocardial infarction. |
| Number of Participants With Ventricular Arrhythmias. | From first dose to end of study, (approximately 260 weeks) | Types of Ventricular Arrhythmias measured in this endpoint will be: Ventricular Tachycardia Ventricular Fibrilation Ventricular Flutter |
| Number of Participants Who Experienced Syncope | From first dose to end of study, (approximately 260 weeks) | Number of participants who experienced syncope. Syncope will be defined as participants who experienced dizziness or orthostatic hypotension. |
| Number of Participants Who Experienced Seizures | From first dose to end of study, (approximately 260 weeks) | Number of participants who were experienced seizures. |
| Number of Participants Who Were Experienced Strokes | From first dose to end of study, (approximately 260 weeks) | Number of participants who were experienced strokes. |
| Number of Participants With a Change in QT and QTcF Intervals. | From first dose to end of study, (approximately 260 weeks) | Number of participants with a change in QTcF intervals. QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR/1000) RR = Respiration rate QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec |
| Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252 | Number of participants with changes of Post-exercise left ventricular outflow tract (LVOT) gradient over time |
| Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252 | Resting left ventricular outflow tract (LVOT) gradient over time |
| Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252 | Post Valsalva left ventricular outflow tract (LVOT) gradient over time |
| Participants With >= 1 NYHA Function Class Improvement | At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252 | Participants with \>= 1 NYHA function class improvement. The NYHA Functional Classification of heart failure assigns participants to 1 of 4 categories based on the participant's symptoms. 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. |
| Mean Change From Baseline in the Overall KCCQ PRO Score. | At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252 | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered 23-item questionnaire questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Overall KCCQ Pro score is the average of all the domains, symptom frequency and symptom burden scores, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status. |
| Mean Change From Baseline in Serum NT-proBNP. | At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252 | Mean change from baseline in Serum N-terminal pro B-type natriuretic peptide levels. |
| Number of Participants Who Received Septal Reduction Therapy | 252 weeks | Number of participants who received septal reduction therapy |
| Plasma Concentration of Mavacamen Overtime | At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252 | Plasma concentration of Mavacamen overtime |
Countries
United States
Participant flow
Pre-assignment details
13 Participants enrolled and treated
Participants by arm
| Arm | Count |
|---|---|
| Mavacamtem Mavacamtem | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other Reasons | 1 |
Baseline characteristics
| Characteristic | Mavacamtem |
|---|---|
| Age, Continuous | 57.8 Years STANDARD_DEVIATION 13.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 5 / 13 |
Outcome results
Primary
Mean Change From Baseline in Serum NT-proBNP.
Mean change from baseline in Serum N-terminal pro B-type natriuretic peptide levels.
Time frame: At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 96 | -1579.1 ng/L | Standard Deviation 2339.95 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 4 | -1017.4 ng/L | Standard Deviation 1540.78 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 8 | -1440.6 ng/L | Standard Deviation 2063.89 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 24 | -1512.8 ng/L | Standard Deviation 2242.4 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 48 | -1579.2 ng/L | Standard Deviation 2328.81 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 72 | -1708.4 ng/L | Standard Deviation 2448.93 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 120 | -1692.7 ng/L | Standard Deviation 2426.02 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 144 | -1507.8 ng/L | Standard Deviation 2407.34 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 156 | -1673.5 ng/L | Standard Deviation 2460.82 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 180 | -1433.6 ng/L | Standard Deviation 2347.72 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 204 | -1568.7 ng/L | Standard Deviation 2400.63 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 228 | -1325.5 ng/L | Standard Deviation 2368.77 |
| Mavacamtem | Mean Change From Baseline in Serum NT-proBNP. | Change from baseline at week 252 | -1681.5 ng/L | Standard Deviation 2409.67 |
Primary
Mean Change From Baseline in the Overall KCCQ PRO Score.
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered 23-item questionnaire questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Overall KCCQ Pro score is the average of all the domains, symptom frequency and symptom burden scores, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status.
Time frame: At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 4 | 5.809 Scores on a Scale | Standard Deviation 8.72 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 8 | 12.304 Scores on a Scale | Standard Deviation 15.7392 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 24 | 16.931 Scores on a Scale | Standard Deviation 18.4502 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 48 | 16.345 Scores on a Scale | Standard Deviation 18.2986 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 72 | 18.600 Scores on a Scale | Standard Deviation 16.7875 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 96 | 16.162 Scores on a Scale | Standard Deviation 18.2376 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 120 | 18.142 Scores on a Scale | Standard Deviation 15.9249 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 144 | 17.860 Scores on a Scale | Standard Deviation 15.5829 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 156 | 18.750 Scores on a Scale | Standard Deviation 15.5701 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 180 | 16.674 Scores on a Scale | Standard Deviation 15.6328 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 204 | 19.661 Scores on a Scale | Standard Deviation 15.9783 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 228 | 91.122 Scores on a Scale | Standard Deviation 10.6882 |
| Mavacamtem | Mean Change From Baseline in the Overall KCCQ PRO Score. | Change from baseline at week 252 | 89.489 Scores on a Scale | Standard Deviation 12.7977 |
Primary
Number of Participants Who Experienced Seizures
Number of participants who were experienced seizures.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Experienced Seizures | 0 Participants |
Primary
Number of Participants Who Experienced Sudden Death
Number of participants who experienced sudden death
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Experienced Sudden Death | 0 Participants |
Primary
Number of Participants Who Experienced Syncope
Number of participants who experienced syncope. Syncope will be defined as participants who experienced dizziness or orthostatic hypotension.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mavacamtem | Number of Participants Who Experienced Syncope | Dizziness | 2 Participants |
| Mavacamtem | Number of Participants Who Experienced Syncope | Orthostatic Hypotension | 1 Participants |
Primary
Number of Participants Who Had Cardiovascular Death
Number of participants who had died due to cardiovascular reasons.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Had Cardiovascular Death | 0 Participants |
Primary
Number of Participants Who Received Septal Reduction Therapy
Number of participants who received septal reduction therapy
Time frame: 252 weeks
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Received Septal Reduction Therapy | 0 Participants |
Primary
Number of Participants Who Were Experienced Myocardial Infarction
Number of participants who experienced myocardial infarction.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Were Experienced Myocardial Infarction | 0 Participants |
Primary
Number of Participants Who Were Experienced Strokes
Number of participants who were experienced strokes.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Were Experienced Strokes | 0 Participants |
Primary
Number of Participants Who Were Hospitalized for Cardiovascular Reasons.
Number of participants who were hospitalized for cardiovascular reasons.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants Who Were Hospitalized for Cardiovascular Reasons. | 1 Participants |
Primary
Number of Participants With a Change in QT and QTcF Intervals.
Number of participants with a change in QTcF intervals. QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR/1000) RR = Respiration rate QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mavacamtem | Number of Participants With a Change in QT and QTcF Intervals. | Post Baseline QTcF > 450msec | 7 Participants |
| Mavacamtem | Number of Participants With a Change in QT and QTcF Intervals. | Post Baseline QTcF > 480msec | 1 Participants |
| Mavacamtem | Number of Participants With a Change in QT and QTcF Intervals. | Post Baseline QTcF > 500msec | 1 Participants |
| Mavacamtem | Number of Participants With a Change in QT and QTcF Intervals. | Change from Baseline QTcF > 30 msec | 2 Participants |
| Mavacamtem | Number of Participants With a Change in QT and QTcF Intervals. | Change from Baseline QTcF > 60 msec | 1 Participants |
Primary
Number of Participants With Heart Failure Due to Systolic Dysfunction, Defined as Asymptomatic LVEF < 50%
Number of participants with heart failure due to systolic dysfunction, defined as asymptomatic LVEF \< 50%
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants With Heart Failure Due to Systolic Dysfunction, Defined as Asymptomatic LVEF < 50% | 0 Participants |
Primary
Number of Participants With LVEF < 50% as Measured by Echocardiography.
Number of participants with LVEF \< 50% as measured by echocardiography.
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mavacamtem | Number of Participants With LVEF < 50% as Measured by Echocardiography. | 2 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events
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. An SAE 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.
Time frame: From first dose to end of treatment + 56 days (Approximately an average of 240 Weeks)
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mavacamtem | Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events | TEAEs | 13 Participants |
| Mavacamtem | Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events | TESAEs | 5 Participants |
Primary
Number of Participants With Ventricular Arrhythmias.
Types of Ventricular Arrhythmias measured in this endpoint will be: Ventricular Tachycardia Ventricular Fibrilation Ventricular Flutter
Time frame: From first dose to end of study, (approximately 260 weeks)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mavacamtem | Number of Participants With Ventricular Arrhythmias. | Torsades De Pointe | 0 Participants |
| Mavacamtem | Number of Participants With Ventricular Arrhythmias. | Ventricular Tachycardia | 1 Participants |
| Mavacamtem | Number of Participants With Ventricular Arrhythmias. | Ventricular Fibrilation | 0 Participants |
| Mavacamtem | Number of Participants With Ventricular Arrhythmias. | Ventricular Flutter | 0 Participants |
Primary
Participants With >= 1 NYHA Function Class Improvement
Participants with \>= 1 NYHA function class improvement. The NYHA Functional Classification of heart failure assigns participants to 1 of 4 categories based on the participant's symptoms. 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.
Time frame: At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 4 | 15.4 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 8 | 46.2 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 24 | 76.9 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 48 | 75.0 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 72 | 90.9 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 96 | 83.3 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 120 | 91.7 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 144 | 91.7 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 156 | 91.7 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 180 | 83.3 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 204 | 83.3 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 228 | 83.3 Percentage of Participants |
| Mavacamtem | Participants With >= 1 NYHA Function Class Improvement | Change from baseline at week 252 | 90.9 Percentage of Participants |
Primary
Plasma Concentration of Mavacamen Overtime
Plasma concentration of Mavacamen overtime
Time frame: At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252
Population: PK Analysis Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 4 | 166.51 ng/mL | Geometric Coefficient of Variation 32.1 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 8 | 334.65 ng/mL | Geometric Coefficient of Variation 21.5 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 24 | 396.18 ng/mL | Geometric Coefficient of Variation 31.7 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 48 | 400.15 ng/mL | Geometric Coefficient of Variation 35.1 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 72 | 407.27 ng/mL | Geometric Coefficient of Variation 24.4 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 96 | 422.82 ng/mL | Geometric Coefficient of Variation 29.3 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 120 | 399.17 ng/mL | Geometric Coefficient of Variation 33.2 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 144 | 410.23 ng/mL | Geometric Coefficient of Variation 42.8 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 156 | 400.02 ng/mL | Geometric Coefficient of Variation 44.1 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 180 | 265.04 ng/mL | Geometric Coefficient of Variation 57.9 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 204 | 376.25 ng/mL | Geometric Coefficient of Variation 69.5 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 228 | 355.29 ng/mL | Geometric Coefficient of Variation 72.3 |
| Mavacamtem | Plasma Concentration of Mavacamen Overtime | Week 252 | 334.57 ng/mL | Geometric Coefficient of Variation 52.1 |
Primary
Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time
Number of participants with changes of Post-exercise left ventricular outflow tract (LVOT) gradient over time
Time frame: At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | < 30 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 50 mmHg | 13 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | < 30 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 30 mmHg to < 50 mmHg | 3 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 50 mmHg | 10 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | < 30 mmHg | 6 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 30 mmHg to < 50 mmHg | 3 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 50 mmHg | 2 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | < 30 mmHg | 8 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 50 mmHg | 3 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | < 30 mmHg | 10 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 50 mmHg | 2 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | < 30 mmHg | 9 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 50 mmHg | 2 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | < 30 mmHg | 9 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 50 mmHg | 2 Participants |
Primary
Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time
Post Valsalva left ventricular outflow tract (LVOT) gradient over time
Time frame: At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | < 30 mmHg | 0 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 50 mmHg | 11 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | < 30 mmHg | 3 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 30 mmHg to < 50 mmHg | 2 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 50 mmHg | 8 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | < 30 mmHg | 9 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 50 mmHg | 2 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | < 30 mmHg | 9 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | < 30 mmHg | 10 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | < 30 mmHg | 9 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 50 mmHg | 3 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | < 30 mmHg | 10 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 50 mmHg | 1 Participants |
Primary
Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time
Resting left ventricular outflow tract (LVOT) gradient over time
Time frame: At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252
Population: Safety Analysis Population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | < 30 mmHg | 3 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 30 mmHg to < 50 mmHg | 2 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Baseline | >= 50 mmHg | 8 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | < 30 mmHg | 8 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 4 | >= 50 mmHg | 5 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | < 30 mmHg | 11 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 48 | >= 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | < 30 mmHg | 11 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 72 | >= 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | < 30 mmHg | 11 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 156 | >= 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | < 30 mmHg | 10 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 30 mmHg to < 50 mmHg | 1 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 204 | >= 50 mmHg | 1 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | < 30 mmHg | 11 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 30 mmHg to < 50 mmHg | 0 Participants |
| Mavacamtem | Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time | Week 252 | >= 50 mmHg | 0 Participants |