Principal Investigator: Omar Wever-Pinzon
Keywords: HCM , Hypertrophic Cardiomyopathy Department: Cardiovascular Medicine
IRB Number: 00117842
Specialty: Cardiology
Sub Specialties: Heart Failure
Recruitment Status: Completed

Contact Information

Jeff  Gibbs
Jeffrey.Gibbs@hsc.utah.edu
801-587-4877

Simple Summary

Primary ObjectiveThe primary objective of this study is:• To assess the long-term safety and tolerability of mavacamten in patients with HCM previously enrolled in 1 of 2 placebo-controlled trials: MAVERICK-HCM (MYK-461-006) IRB_00109286 or EXPLORER-HCM (MYK-461-005) IRB_00105785.Note :University of Utah is a participating site for both trials ( MAVERICK_HCM and EXPLORER_HCM ) Secondary ObjectivesThe secondary objective of this study is:• To assess in the above population the long-term effects of mavacamten on symptoms and echocardiographic measures of cardiac functionTo assess LVOT obstruction as determined by Doppler echocardiography in theEXPLORER-LTE cohortExploratory ObjectivesThe exploratory objectives of this study are:• To assess the long-term effects of mavacamten on disease biomarkers• To assess the effect of mavacamten on arterial pulse wave morphology inMAVERICK-LTE cohort only• To assess the long-term effects of mavacamten on patient-reported outcomes (PRO)in EXPLORER-LTE cohort only• To assess the PK characteristics of mavacamten Pharmacokinetic ObjectiveThe PK objective of this study is:• To perform population PK analyses in the above population Cardiac Magnetic Resonance Imaging Substudy ObjectiveThe cardiac magnetic resonance imaging (CMR) substudy objective is:• To assess the effects of mavacamten on cardiac mass and structure as evaluated by CMR

Inclusion Criteria

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)

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); 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 (ALT) or aspartate aminotransferase (AST)

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,lactating, or breast feeding 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)

Exclusion Criteria

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 Fridericia-corrected QT interval 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

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

 

CMR Substudy Inclusion/ Exclusion Criteria

Each participant must meet the inclusion/exclusion criteria and be enrolled in the
MYK-461-007 study.
In addition to the scheduled assessments at these visits, sites must also collect height, weight
and hematocrit if not already performed.
Participants from the MAVERICK-HCM study may participate in the CMR substudy.
Participants from the EXPLORER-HCM study must have already participated in the CMR
substudy.
In addition, to be included in this substudy participants must not have:
1. An ICD or pacemaker
2. Atrial fibrillation at the time of scheduled day of CMR.

 

Participant Reimbursement

Screening75Day 1100Wk 4100Wk 650 ( MAVERICK Cohort only )Wk 8100Wk 12100Wk 16100Wk 1825Wk 24100Wk 3025Wk 36100Wk 4225Wk 48100Wk 60100Wk 6625Wk 72100Wl 7825Wk 84100Wk 9025Wk 96100Wk 10025Wk 104100