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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 10 December 2019
Main ID:  EUCTR2018-004039-64-DK
Date of registration: 13/06/2019
Prospective Registration: Yes
Primary sponsor: MyoKardia, Inc.
Public title: 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)
Scientific title: 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) - MAVA-LTE
Date of first enrolment: 30/09/2019
Target sample size: 280
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004039-64
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: no
Randomised: no
Open: yes
Single blind:
Double blind:
Parallel group:
Cross over:
Other:
If controlled, specify comparator, Other Medicinial Product:
Placebo:
Other:
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Czech Republic Denmark France Germany Israel Italy Netherlands
Poland Portugal Spain United Kingdom United States
Contacts
Name: Clinical Trial or Medical Inquiries   
Address:  333 Allerton Avenue 94080 South San Francisco, CA United States
Telephone: 16507410900
Email: medinfo@myokardia.com
Affiliation:  MyoKardia, Inc.
Name: Clinical Trial or Medical Inquiries   
Address:  333 Allerton Avenue 94080 South San Francisco, CA United States
Telephone: 16507410900
Email: medinfo@myokardia.com
Affiliation:  MyoKardia, Inc.
Key inclusion & exclusion criteria
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 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)
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 238
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

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 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Hypertrophic Cardiomyopathy
MedDRA version: 20.0 Level: PT Classification code 10020871 Term: Hypertrophic cardiomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Intervention(s)

Product Name: Mavacamten
Product Code: MYK-461
Pharmaceutical Form: Capsule
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: MYK-461
Other descriptive name: MAVACAMTEN
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 15-

Product Name: Mavacamten
Product Code: MYK-461
Pharmaceutical Form: Capsule
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: MYK-461
Other descriptive name: MAVACAMTEN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Mavacamten
Product Code: MYK-461
Pharmaceutical Form: Capsule
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: MYK-461
Other descriptive name: MAVACAMTEN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Mavacamten
Product Code: MYK-461
Pharmaceutical Form: Capsule
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: MYK-461
Other descriptive name: MAVACAMTEN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Primary end point(s): 12.3.2 Efficacy and Pharmacodynamic Endpoints
1 Change from baseline in echocardiographic parameters of systolic function (eg, LVEF) and diastolic function (eg, peak velocity of early diastolic septal and lateral mitral annular motion [e?], ratio of peak velocity of early diastolic transmitral flow [E] to e? [E/e?], ratio of E to peak velocity of late transmitral flow [A] [E/A], pulmonary artery systolic pressure, left atrium size) over time
2 Change from baseline in resting and post-Valsalva LVOT gradient (EXPLORER-HCM participants only)
3 Change from baseline in NYHA functional class over time
4 Change from baseline in NT-proBNP over time
5 Frequency of cardiac transplantation

Secondary Objective: • To assess in the MAVERICK-LTE and EXPLORER-LTE cohorts the long-term effects of mavacamten on symptoms and echocardiographic measures of cardiac function
• To assess LVOT obstruction as determined by Doppler echocardiography in the EXPLORER-LTE cohort

Timepoint(s) of evaluation of this end point: 1 Week 96/EOT
2 Week 96/EOT
3 Week 96/EOT
4 Week 96/EOT
5 EOT
Main Objective: • To assess the long-term safety and tolerability of mavacamten in participants with HCM previously enrolled in 1 of 2 placebo-controlled trials: MAVERICK-HCM for nHCM and EXPLORER-HCM for oHCM.
Secondary Outcome(s)

Secondary end point(s): CMR Substudy -
For Participants from EXPLORER-HCM
Primary Endpoint
• Change from Week 24 to Week 96 in LV mass index
Exploratory Endpoints
• Change from Week 24 to Week 96 in myocardial fibrosis as measured by late gadolinium enhancement
• Change from Week 24 to Week 96 in cellular hypertrophy, left atrial volume and function, and LV function

For Participants from MAVERICK-HCM
Primary Endpoint
• Change from baseline to Week 96 in LV mass index
Exploratory Endpoints
• Change from baseline to Week 96 in myocardial fibrosis as measured by late gadolinium enhancement
• Change from baseline to Week 96 in cellular hypertrophy, left atrial volume and function, and LV function
Timepoint(s) of evaluation of this end point: Week 96
Secondary ID(s)
2018-004039-64-NL
MYK-461-007
Source(s) of Monetary Support
MyoKardia, Inc.
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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