A Long-term Safety Extension Study of Mavacamten (MYK-461) in Adults with Hypertrophic Cardiomyopathy Who Have Completed the MAVERICKHCM (MYK-461-006) or EXPLORER-HCM (MYK-461-005) Trials (MAVA-LTE)
- Conditions
- Heart muscle diseaseinherited hart disease10007510
- Registration Number
- NL-OMON54979
- Lead Sponsor
- MyoKardia, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
1. Has completed the Parent Study through to the EOS Visit within
90 days of signing consent. (Participants who are beyond the 90
day window from EOS Visit may be included in this study
pending MyoKardia Medical Monitor approval). Participants who prematurely
discontinued
from the Parent Study or the MAVA LTE study may be considered for
inclusion.
2. Is able to understand and comply with the study procedures,
understand the risks involved in the study, and provide informed
consent according to federal, local, and institutional guidelines
before the first study-specific procedure
3. Body weight is greater than 45 kg at the Screening Visit or Day 1
(Day 1 weight must be verified prior to dosing)
4. Has adequate acoustic windows to enable accurate TTEs (refer to
Echocardiography Site Instruction Manual)
5. Has documented LVEF >= 50% by echocardiography core
laboratory read of screening TTE at rest
6. Has safety laboratory parameters within normal limits (according
to the central laboratory reference range); however, a participant
with safety laboratory parameters outside normal limits may be
included if he or she meets all of the following criteria:
• The safety laboratory parameter outside normal limits is
considered by the Investigator to be clinically unimportant
• If there is an alanine aminotransferase or aspartate
aminotransferase result, the value must be < 3× the upper limit
of the laboratory reference range
• The body size-adjusted estimated glomerular filtration rate is
>= 30 mL/min/1.73 m2
7. Female participants must not be pregnant or lactating and, if
sexually active, must use one of the following highly effective
birth control methods from the Screening Visit through 90 days
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 (FSH) levels are in the postmenopausal
range.
• In addition to the above contraceptive requirements for female
participants, male partners must also use a contraceptive (eg,
barrier, condom, or vasectomy)
1. Has persistent or permanent atrial fibrillation not on
anticoagulation for at least 4 weeks prior and/or is not adequately
rate-controlled
(Note: participants with persistent or permanent atrial fibrillation
who are anticoagulated and adequately rate-controlled are
allowed)
2. Is currently taking, or has taken within 14 days of Screening, a
prohibited medication such as a cytochrome P450 (CYP) 2C19
inhibitor (eg, omeprazole), a strong CYP 3A4 inhibitor, or St.
John*s Wort (see APPENDIX 2 for more details)
3. Has QTcF > 500 ms at Screening or any other ECG abnormality
considered by the Investigator to pose a risk to participant safety
(eg, second degree atrioventricular block type II)
4. Has documented obstructive coronary artery disease (> 70%
stenosis in one or more epicardial coronary arteries) or history of
myocardial infarction
5. Has known moderate or severe (as per Investigator*s judgment)
aortic valve stenosis at Screening Visit
6. Has hypersensitivity to any of the components of the mavacamten
formulation
7. Has participated in a clinical trial in which the participant received
any investigational drug (or is currently using an investigational device)
within 30 days prior to Screening, or at least 5 times the respective
elimination half life (whichever is longer), except for participation in
MAVERICK-HCM or EXPLORER-HCM. Prior participation in a noninterventional
observational study is
allowed.
8. Has a history of syncope or a history of sustained ventricular
tachyarrhythmia with exercise between Parent Study EOS Visit and
Screening
Visit.
9. Has a history of resuscitated sudden cardiac arrest or known history
of appropriate implantable cardioverter-defibrillator (ICD) discharge for
life-threatening ventricular arrhythmia between Parent Study EOS Visit
and Screening
Visit.
(Note: history of anti-tachycardia pacing (ATP) is
allowed)
10. Currently treated with disopyramide or ranolazine (within 14 days
prior to Screening Visit) or treatment with disopyramide or ranolazine is
planned during the
study
11. Currently treated or planned treatment during the study with a
combination of beta blocker and verapamil or a combination of beta
blocker and
diltiazem
12. Has any 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 and safety assessments in
the
study
13. History of clinically significant malignant disease that developed
since enrollment in the Parent
Study
• Participants who have been successfully treated for nonmetastatic
cutaneous squamous cell or basal cell carcinoma or have been
adequately treated for cervical carcinoma in situ or breast ductal
carcinoma in situ (DCIS) can be included in the
study
14. Is unable to comply with the study requirements, including the
number of required visits to the clinical site
15. Is employed by or is a relative of someone employed by MyoKardia,
the Investigator, or his/her staff or family
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety<br /><br>• Incidence of major adverse cardiac events (death, stroke, acute myocardial<br /><br>infarction)<br /><br>• Incidence of hospitalizations (both cardiovascular [CV] and non-CV)<br /><br>• Incidence of heart failure (HF) events (includes HF hospitalizations and<br /><br>urgent emergency room/outpatient visits for HF)<br /><br>• Incidence of atrial fibrillation/flutter (new from Screening Visit)<br /><br>• Incidence of ICD discharges and resuscitated cardiac arrest<br /><br>• Incidence of ventricular tachyarrhythmias (includes ventricular tachycardia,<br /><br>ventricular fibrillation)<br /><br>• Incidence of any AE potentially linked to QT prolongation (Torsade de<br /><br>pointes, CV or sudden death, sustained ventricular tachycardia, ventricular<br /><br>fibrillation and flutter, syncope, and seizures)<br /><br>• Frequency and severity of treatment-emergent AEs, treatmentemergent serious<br /><br>AEs, and laboratory abnormalities (including trends in NT-proBNP)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Efficacy and Pharmacodynamics<br /><br>• Change from baseline in echocardiographic parameters of systolic function<br /><br>(eg, LVEF) and diastolic function (eg, peak velocity of early diastolic septal<br /><br>and lateral mitral annular motion [e*], ratio of peak velocity of early<br /><br>diastolic transmitral flow [E] to e* [E/e*], ratio of E to peak velocity of late<br /><br>transmitral flow [A] [E/A], pulmonary artery systolic pressure, left atrium<br /><br>size) over time<br /><br>• Change from baseline in resting and post-Valsalva LVOT gradient (EXPLORER-HCM<br /><br>participants only)<br /><br>• Change from baseline in New York Heart Association (NYHA) functional class<br /><br>over time<br /><br>• Change from baseline in NT-proBNP over time<br /><br>• Frequency of cardiac transplantation </p><br>