A Randomized, Double blind, Placebo controlled Clinical Study to Evaluate Mavacamten (MYK-461) in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy
- Conditions
- Heart muscle diseaseinherited hart disease10007510
- Registration Number
- NL-OMON50292
- Lead Sponsor
- MyoKardia, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1.Able to understand and comply with the study procedures, understand
the risks involved in the study, and provide written informed consent
according to federal, local, and institutional guidelines before the first
study specific procedure
2.Is at least 18 years old at Screening
3.Body weight is greater than 45 kg at Screening
4.Has adequate acoustic windows to enable accurate TTEs
5.Diagnosed with oHCM consistent with current AACF/AMA and ESC, ie, satisfy
both criteria below (criteria
to be documented by the echocardiography core laboratory):
A.Has unexplained left ventricular (LV) hypertrophy with nondilated
ventricular chambers in the absence of other cardiac (eg, hypertension,
aortic stenosis) or systemic disease and with maximal LV wall thickness
*15 mm (or *13 mm with positive family history of hypertrophic
cardiomyopathy [HCM]), as determined by core lab interpretation and
B.Has LVOT peak gradient *50 mmHg during Screening as assessed by
echocardiography at rest, after Valsalva maneuver, or postexercise
(confirmed by echocardiography core laboratory interpretation)
6.Has documented left ventricular ejection fraction (LVEF) *55% by
echocardiography core laboratory read of Screening TTE at rest
7. Has LVOT gradient with Valsalva maneuver at screening TTE of *30mmHg,
determined by echocardiography core laboratory.
8.Has New York Heart Association (NYHA) functional Class II or III symptoms at
Screening
9.Has documented oxygen saturation at rest *90% at Screening
10.Is able to perform an upright CPET and has a respiratory exchange
ratio (RER) *1.0 at Screening per central reading; if the RER is between
0.91 and 1.0, the participant may be enrolled only if it is determined by
the central CPET laboratory that peak exercise has been achieved in the
subject (the only permitted reasons for subpeak performance are [1] a
decrease in systolic blood pressure or [2] severe angina as described in
the CPET Laboratory Manual)
11.Female participants must not be pregnant or lactating and, if sexually
active, must be using one of the following highly effective birth control
methods from the Screening visit through 3 months after the last dose of
investigational medicinal product (IMP). Combined (estrogen-and
progestogen-containing) hormonal contraception associated with inhibition of
ovulation or progestogen-only hormonal contraception associated with inhibition
of ovulation by oral, implantable, or injectable route of administration.
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- Female is surgically sterile for 6 months or postmenopausal for 1 year.
Permanent sterilization includes hysterectomy, bilateral oophorectomy,
bilateral salpingectomy, and/or documented bilateral tubal occlusion at
least 6 months prior to Screening. Females are considered
postmenopausal if they have had amenorrhea for at least 1 year or
more following cessation of all exogenous hormonal treatments and
follicle stimulating hormone levels are in the postmenopausal range
Male partners must also use a contraceptive (eg barrier, condom or vasectomy)
1.Previously participated in a clinical study with mavacamten
2.Hypersensitivity to any of the components of the mavacamten
formulation
3.Participated in a clinical trial in which the participant received any
investigational drug (or is currently using an investigational device)
within 30 days of Screening, or at least 5x the respective elimination half
life (whichever is longer)
4.Infiltrative or storage disorder causing CH that mimics oHCM, such as
Fabry disease, amyloidosis, or Noonan syndrome with LVH
5.Medical condition that precludes upright exercise stress testing
6.History of syncope within 6 months prior to Screening or history of sustained
VT with exercise within 6 months prior
to Screening
7.History of resuscitated sudden CA (at any time) or history of
appropriate ICD discharge/shock for life-threatening VA within 6 months prior
to Screening
8.Has paroxysmal, intermittent AF with AF present per the investigator's
evaluation of the participant's ECG at time of Screening
9.Has persistent/permanent AF not on anticoagulation for at least 4
weeks to Screening &/or not adequately rate controlled within 6 months
prior to Screening
10.Current treatment (within 14 days to Screening) or planned
treatment during the study with disopyramide or ranolazine
11.Current treatment (within 14 days prior to Screening) or planned
treatment during the study with a combination of *-blockers and
verapamil or a combination of *-blockers and diltiazem
12.Individuals on *-blockers, verapamil, or diltiazem, any dose
adjustment of that medication <14 days to Screening or any anticipated
change in treatment regimen using these medications during the study
13.Successfully treated with ISR (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
14.ICD placement or pulse generator change whithin 2 months prior to Screening
or planned new ICD placement during study
15.Has QT interval with Fridericia correction (QTcF) >500 ms at screening or
other
ECG abnormality considered by investigator to pose risk to participant
safety (eg, second-degree atrioventricular block type II)
16.Documented OCAD (>70% stenosis in one or more epicardial
coronary arteries) or history of MI
17.Moderate or severe (as per investigator's judgment) AVS at
Screening
18.Acute or serious comorbid condition (eg, major infection or
hematologic, renal, metabolic, gastrointestinal, or endocrine
dysfunction) that, in the judgment of the investigator, could lead to
premature termination of study participation or interfere with the
measurement or interpretation of the efficacy & safety assessments in
the study
19.Has pulmonary disease that limits exercise capacity or systemic
arterial oxygen saturation
20.History of malignant disease within 10 years of
Screening:
21.Has safety laboratory parameters (chemistry, hematology,
coagulation, & urinalysis) outside normal limits (according to the central
laboratory reference range) at Screening as assessed by the central
laboratory; however, participant with safety laboratory parameters
outside normal limits may be included if he or she meets all of the
following criteria:
*Safety laboratory parameter outside normal limits is considered by the
investigator to be clinical
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* Clinical response defined as achieving (1) an improvement of at least 1.5<br /><br>mL/kg/min or more in peak oxygen consumption (pVO2) as determined by CPET and a<br /><br>reduction of one or more class in NYHA Functional Classification or 2) an<br /><br>improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA<br /><br>Functional Class. </p><br>
- Secondary Outcome Measures
Name Time Method <p>* Change from baseline to Week 30 in post-exercise LVOT peak gradient<br /><br>* Proportion of participants with at least 1 class improvement in NYHA<br /><br>functional class from baseline to Week 30<br /><br>* Change from baseline to Week 30 in peak oxygen consumption (pVO2) as<br /><br>determined by CPET<br /><br>* Change from baseline to Week 30 in participant-reported health-related<br /><br>quality of life as assessed by the KCCQ score<br /><br>* Change from baseline to Week 30 in patient-reported severity of HCM symptoms<br /><br>as assessed by the HCM Symptom Questionnaire score</p><br>