Clinical Study to Evaluate Mavacamten (MYK-461) in Adults... | NCT03470545

Label	Type	Description	Intervention Names
mavacamten (MYK-461)	Experimental		Drug: mavacamten
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
mavacamten	Drug	mavacamten capsules	mavacamten (MYK-461)	MYK-461

Measure	Description	Time Frame
Percentage of Participants Achieving A Clinical Response	A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.	30 weeks

Measure	Description	Time Frame
Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.	The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the Cardiovascular Imaging Core Laboratory (CICL, Boston MA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Age 18 and greater, body weight ≥ 45kg
Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs)
Diagnosed with oHCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines and satisfy both criteria:
Has documented left ventricular ejection fraction (LVEF) ≥55%
NYHA Class II or III
Has documented oxygen saturation at rest ≥90% at Screening
Is able to perform an upright CPET and has a respiratory exchange ratio (RER) ≥1.0 at Screening per central reading

Key Exclusion Criteria:

Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to Screening
History of resuscitated sudden cardiac arrest (at any time) or known history of appropriate implantable cardioverter defibrillator (ICD) discharge for life-threatening ventricular arrhythmia within 6 months prior to Screening
Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at Screening
Persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate controlled within 6 months prior to Screening
Treatment (within 14 days prior to Screening) or planned treatment during the study with disopyramide or ranolazine
Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of β-blockers and calcium channel blockers
LVOT gradient with Valsalva maneuver <30 mmHg at Screening
Has been successfully treated with invasive septal reduction (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
ICD placement within 2 months prior to Screening or planned ICD placement during the study
Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
Prior treatment with cardiotoxic agents such as doxorubicin or similar

Name	Affiliation	Role
Medical Information Team	MyoKardia, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Arizona		Scottsdale	Arizona	85259	United States
Cedars-Sinai Medical Center (Smidt Heart Institute)

PubMed Identifier	Type	Citation	Retractions
42251960	Derived	Saberi S, Naidu SS, Olivotto I, Hagege AA, Zhong Y, Lam J, Wyrwich KW, Fine JT, Dolan C, Allen V, Sehnert AJ, Reaney M. Impact of Mavacamten on Disease-Related Symptoms in Patients With Obstructive Hypertrophic Cardiomyopathy: HCMSQ Outcomes in EXPLORER-HCM. J Card Fail. 2026 Jun 6:S1071-9164(26)00257-5. doi: 10.1016/j.cardfail.2026.03.036. Online ahead of print.
39653325

ID	Title	Description
FG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 4, 2019	May 7, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving A Clinical Response

A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.

Posted

Count of Participants

Participants

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Units	Counts
Participants	OG000123 OG001128

Title

Denominators

Categories

Title	Measurements
	OG00045 OG00122

Secondary

Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.

The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the Cardiovascular Imaging Core Laboratory (CICL, Boston MA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.

Posted

Mean

Standard Deviation

mmHg

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Units	Counts

Secondary

Change From Baseline to Week 30 in pVO2 as Assessed by CPET

Cardiopulmonary exercise testing (CPET) was performed at baseline and week 30 following a study-specified protocol and peak oxygen consumption (pVO2) was determined by the Cardiovascular Metabolic Disease Research Institute (CMDRI, Palo Alto, CA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.

Posted

Mean

Standard Deviation

mL/kg/min

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Units	Counts

Secondary

Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30

New York Heart Association (NYHA) functional classification was determined by the principal investigator at baseline and at specified timepoints in the study. At baseline, all subjects were NYHA Class II or III. For the secondary outcome, NYHA class at Week 30 was compared to baseline and the proportion of subjects with an improvement of at least one class was determined, and the difference between treatment groups was analyzed. The proportion was also multiplied by 100 to provide the result as a percent.

Posted

Count of Participants

Participants

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Secondary

Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score. The instrument utilizes a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life. The KCCQ clinical summary (KCCQ-CS) score, a prespecified secondary outcome of EXPLORER-HCM, combines the physical limitation and total symptom scores.

Posted

Mean

Standard Deviation

Scores on Scale

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Secondary

Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score

The Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) is a patient reported outcome instrument that is a daily self-administered 11-item questionnaire. The HCMSQ assesses the core symptoms of HCM (tiredness/fatigue, heart palpitations, chest pain, dizziness, and shortness of breath). The Shortness of Breath domain score, a pre-specified secondary outcome of EXPLORER-HCM, assesses the frequency and severity of shortness of breath. The minimum score = 0 and maximum score = 18 where lower score indicates better health status. There are no units to the score.

Posted

Mean

Standard Deviation

Scores on Scale

30 weeks

ID	Title	Description
OG000	Mavacamten (MYK-461)	Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.
OG001	Placebo	Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial Fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected123 at risk EG0015 affected128 at risk
Stress cardiomyopathy	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected123 at risk EG0010 affected128 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Cardiac Failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Cardiogenic shock	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Pericardial effusion	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Systolic dysfunction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Atrial septal defect	Congenital, familial and genetic disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Sudden Death	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0012 affected128 at risk
Bacterial colitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Diverticulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Forearm Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
SLE	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Cholesteatoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected123 at risk EG0011 affected128 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk
Device inappropriate shock delivery	Product Issues	MedDRA 21.0	Systematic Assessment	EG0001 affected123 at risk EG0010 affected128 at risk
Vocal cord polyp	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected123 at risk EG0011 affected128 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial Fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected123 at risk EG00110 affected128 at risk
Palpitations	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected123 at risk EG00110 affected128 at risk
Angina pectoris	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected123 at risk EG0017 affected128 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected123 at risk EG00113 affected128 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected123 at risk EG0014 affected128 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00026 affected123 at risk EG00117 affected128 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected123 at risk EG00110 affected128 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected123 at risk EG0012 affected128 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected123 at risk EG0017 affected128 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected123 at risk EG0017 affected128 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected123 at risk EG0013 affected128 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected123 at risk EG0018 affected128 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected123 at risk EG0012 affected128 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00015 affected123 at risk EG00119 affected128 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00010 affected123 at risk EG0016 affected128 at risk

ID	Title	Description
BG000	Mavacamten (MYK-461)	mavacamten: mavacamten capsules
BG001	Placebo	Placebo: placebo oral capsule
BG002	Total	Total of all reporting groups

ID	Term
D009202	Cardiomyopathies
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D001020	Aortic Stenosis, Subvalvular
D001024	Aortic Valve Stenosis
D000082862	Aortic Valve Disease
D006349	Heart Valve Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Mavacamten (MYK-461)	mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	0	123	14	123	108	123
EG001	Placebo	Placebo: placebo oral capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient. Placebo dose to match mavacamten capsule was administered once daily by mouth.	1	128	12	128	104	128