A Long-term Safety Extension Study of Mavacamten (MYK-461) in Adults with Hypertrophic Cardiomyopathy Who Have Completed the MAVERICK-HCM (MYK-461-006) or EXPLORER-HCM (MYK-461-005) Trials (MAVA-LTE)
- Conditions
- Hypertrophic CardiomyopathyMedDRA version: 20.0Level: PTClassification code 10020871Term: Hypertrophic cardiomyopathySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-004039-64-CZ
- Lead Sponsor
- MyoKardia, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
days of signing consent. (Participants who are beyond the 90 day
window from the EOS Visit may be included in this study pending
MyoKardia Medical Monitor approval). Participation 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 the
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 4 months after the last dose of
investigational medicinal product (IMP).
• combined (estrogen- and progestogen-containing) hormonal
contraception associated with inhibition of ovulation or progestogenonly
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.
In addition to the above contraceptive requirements for female
participants, male partners must also use a contraceptive (eg, barrier,
condom, or vasectomy)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 208
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42
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 CYP2C19 inhibitor (eg, omeprazole), a
strong CYP3A4 inhibitor, or St. John's Wort (see APPENDIX 2 for more details)
3. Has any 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 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 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method