Cardiomyopathy, Hypertrophic Obstructive
Conditions
Keywords
Mavacamten, Obstructive Hypertrophic Cardiomyopathy (HCM)
Brief summary
The purpose of this study is to evaluate the effectiveness, safety, and tolerability of a 30-week course of mavacamten and the long-term effects of mavacamten in Japanese participants with symptomatic obstructive hypertrophic cardiomyopathy (HCM).
Interventions
DRUGMavacamten
Specified dose on specified days
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
Yes
Inclusion criteria
* Age 18 and greater, body weight ≥ 35kg * Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs) * Diagnosed with obstructive hypertrophic cardiomyopathy consistent with current American College of Cardiology Foundation/American Heart Association, European Society of Cardiology, and Japanese Circulation Society guidelines * Has documented left ventricular ejection fraction (LVEF) ≥60% NYHA Class II or III
Exclusion criteria
* Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy * History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to Screening * History of resuscitated sudden cardiac arrest (at any time) or known history of appropriate implantable cardioverter defibrillator (ICD) discharge for life-threatening ventricular arrhythmia within 6 months prior to Screening * Paroxysmal atrial fibrillation with atrial fibrillation present at the time of Screening. * Persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate controlled within 6 months prior to Screening * Treatment (within 14 days prior to Screening) or planned treatment during the study with cibenzoline, disopyramide or ranolazine * Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of beta blockers and verapamil or a combination of beta blockers and diltiazem * Has been successfully treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\]) within 6 months prior to Screening or plans to have either of these treatments during the study * ICD placement within 2 months prior to Screening or planned ICD placement during the study * Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation procedures, or completion * Prior treatment with cardiotoxic agents such as doxorubicin or similar Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30 | At Baseline and Week 30 | The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the doppler echocardiography. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30 | At Baseline and Week 30 | 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. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment. |
| Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30 | Baseline and at Week 30 | The NYHA Functional Classification of Heart Failure (HF) assigns participants to 1 of 4 categories based on the participant's symptoms. Class I (No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea); Class II (Slight limitation of physical activity, Comfortable at rest, Ordinary physical activity results in fatigue, palpitation, dyspnea); Class III (Marked limitation of physical activity, Comfortable at rest, Less-than ordinary-activity causes fatigue, palpitation, or dyspnea) and Class IV (Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases). Improvement is defined as participant moving to lower class category from a higher one. Baseline is defined as last non-missing measurement prior to the first dose. |
| Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30 | At baseline and week 30 | Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose. |
| Change From Baseline in Cardiac Troponin I at Week 30 | At baseline and week 30 | Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment. |
| Change From Baseline in Cardiac Troponin T at Week 30 | At baseline and week 30 | Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment. |
Countries
Japan
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mavacamten Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg. | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | Mavacamten |
|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 10.95 |
| Race/Ethnicity, Customized Japanese | 38 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 20 / 38 |
| serious Total, serious adverse events | 6 / 38 |
Outcome results
Primary
Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30
The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the doppler echocardiography. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Time frame: At Baseline and Week 30
Population: Intent-to-treat population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mavacamten | Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30 | -60.6963 millimeters of mercury (mmHg) | Standard Deviation 31.55674 |
Secondary
Change From Baseline in Cardiac Troponin I at Week 30
Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Time frame: At baseline and week 30
Population: Intent to Treat population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mavacamten | Change From Baseline in Cardiac Troponin I at Week 30 | -10.920 ng/L |
Secondary
Change From Baseline in Cardiac Troponin T at Week 30
Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Time frame: At baseline and week 30
Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mavacamten | Change From Baseline in Cardiac Troponin T at Week 30 | -4.95 ng/L |
Secondary
Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30
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. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Time frame: At Baseline and Week 30
Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mavacamten | Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30 | 9.766 Score on a Scale | Standard Deviation 16.8588 |
Secondary
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30
Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose.
Time frame: At baseline and week 30
Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mavacamten | Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30 | -738.0 nanogram per liter (ng/L) |
Secondary
Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30
The NYHA Functional Classification of Heart Failure (HF) assigns participants to 1 of 4 categories based on the participant's symptoms. Class I (No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea); Class II (Slight limitation of physical activity, Comfortable at rest, Ordinary physical activity results in fatigue, palpitation, dyspnea); Class III (Marked limitation of physical activity, Comfortable at rest, Less-than ordinary-activity causes fatigue, palpitation, or dyspnea) and Class IV (Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases). Improvement is defined as participant moving to lower class category from a higher one. Baseline is defined as last non-missing measurement prior to the first dose.
Time frame: Baseline and at Week 30
Population: Intent To Treat Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mavacamten | Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30 | 63.2 Percentage of participants |