Cardiomyopathy, Hypertrophic
Conditions
Keywords
Mavacamten, non-obstructive HCM, non-obstructive hypertrophic cardiomyopathy (nHCM)
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of mavacamten compared with placebo in participants with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM).
Interventions
DRUGMavacamten
Specified dose on specified days
OTHERPlacebo
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines: unexplained left-ventricular hypertrophy with non-dilated ventricular chambers in the absence of other cardiac or systemic disease which can produce the required magnitude of hypertrophy of a maximal left ventricular (LV) wall thickness ≥ 15 millimeters (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy \[HCM\]) as determined by core laboratory interpretation. * Peak left ventricular outflow tract (LVOT) pressure gradient \< 30 millimeters mercury (mm Hg) at rest and \< 50 mm Hg with provocation (Valsalva maneuver and stress echocardiography). * New York Heart Association (NYHA) Class II or III.
Exclusion criteria
* Known infiltrative or storage disorder causing cardiac hypertrophy that mimics non-obstructive hypertrophic cardiomyopathy (nHCM) such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy. * History of unexplained syncope within 6 months prior to screening. * History of sustained ventricular tachyarrhythmia (\> 30 seconds) within 6 months prior to screening. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in KCCQ-23 CSS at Week 48 | From First dose to week 48 | 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. |
| Change From Baseline in pVO2 at Week 48 | From First dose to week 48 | Clinically meaningful mean change from baseline(1.4ml/kg/min) of pVO2 at Week 48. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in VE/VCO2 Slope at Week 48 | From First dose to week 48 | VE/VCO₂ slope was assessed using cardiopulmonary exercise testing (CPET). The slope was calculated as the linear regression of minute ventilation (VE) against carbon dioxide production (VCO₂). A decrease in VE/VCO₂ slope reflects improved ventilatory efficiency. |
| Mean Change From Baseline in NT-proBNP to Week 48 | From First dose to week 48 | Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose. |
| Percentage of Participants With at Least 1 Class of NYHA Improvement From Baseline at Week 48 | From First dose to week 48 | 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 HCMSQ SoB Domain Score at Week 48 | From First dose to week 48 | The HCMSQ is a self- administered, 9-item questionnaire that assesses the core symptoms of HCM (shortness of breath, tiredness/fatigue, heart palpitations, chest pain, dizziness, and syncope). At each visit, a 7-day period will be defined, ending on the last day with a non-missing HCMSQ score prior to the actual clinic visit (or first dose date if baseline). If the participant completes the HCMSQ for 4 or more days within this period, the weekly average HCMSQ score will be calculated. If fewer than 4 days are completed, other 7-day periods will be considered. For baseline, any 7-day period with at least 4 days of HCMSQ prior to the first dose or randomization date (if first dose date is missing) will be used. Each domain of the SoB scale is scored 1 to 6. The scores are added together to give a total score. Lower scores indicating low to no shortness of breath, higher scores indicating frequent episodes of shortness of breath. the lower the score the better. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, Norway, Poland, Portugal, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
580 participants randomized and treated
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.4 Years STANDARD_DEVIATION 14.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 222 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 61 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 90 Participants |
| Race (NIH/OMB) Black or African American | 14 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 | 33 Participants |
| Race (NIH/OMB) White | 400 Participants |
| Sex: Female, Male Female | 266 Participants |
| Sex: Female, Male Male | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 34 | 1 / 19 | 1 / 254 | 2 / 271 |
| other Total, other adverse events | 26 / 34 | 17 / 19 | 201 / 254 | 192 / 271 |
| serious Total, serious adverse events | 18 / 34 | 8 / 19 | 63 / 254 | 55 / 271 |
Outcome results
None listed