Obstructive Hypertrophic CardiomyopathyPhase 3EXPLORER-HCMNCT03470545
Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
A Phase 3 study testing mavacamten in people with Obstructive Hypertrophic Cardiomyopathy, run by MyoKardia, Inc. at 71 sites in 13 countries.
Trial summary
This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obstructive Hypertrophic Cardiomyopathy
- What is being tested?
- mavacamten
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 251 participants
- Where
- 71 sitesin 13 countries
- Study dates
- 29 May 2018to 6 May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
71 sites in 13 countries.
71 sites in 13 countries
United States29 sites
University of Michigan
Ann Arbor, Michigan, 48109
St. Luke's Cardiology Associates
Bethlehem, Pennsylvania, 18018
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Carolinas Medical Center
Charlotte, North Carolina, 28203
University of Virginia Health System
Charlottesville, Virginia, 22903
Northwestern University
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas Southwestern Medical Center
Dallas, Texas, 75235
Duke Cardiology at Southpoint
Durham, North Carolina, 27710
Spectrum Health
Grand Rapids, Michigan, 49512
Houston Methodist Hospital
Houston, Texas, 77030
University of Texas Houston Medical School
Houston, Texas, 77030
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242
Mayo Clinic Jacksonville - PPDS
Jacksonville, Florida, 32224
Cedars-Sinai Medical Center (Smidt Heart Institute)
Los Angeles, California, 90048
Methodist University Hospital
Memphis, Tennessee, 38163
Yale New Haven Hospital
New Haven, Connecticut, 16511
NYU Langone Medical Center
New York, New York, 10017
Columbia University Medical Center
New York, New York, 10032
University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center Presbyterian
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
Intermountain Medical Center
Salt Lake City, Utah, 84107
University of Utah
Salt Lake City, Utah, 84132
UCSF School of Medicine
San Francisco, California, 94143
Mayo Clinic Arizona
Scottsdale, Arizona, 85259
University of Washington Medical Center
Seattle, Washington, 98195
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
Germany7 sites
Kerckhoff-Klinik-Forschungs-GmbH
Bad Nauheim, 61231
Charité Campus Buch - Experimental and Clinical Research Center
Berlin, 13125
Charité - Universitätsmedizin Berlin
Berlin, 13353
Cardiologicum Dresden und Pirna
Dresden, 01277
University Medicine Göttingen
Göttingen, Neidersachsen
University Clinic Heidelberg - PPDS
Heidelberg, 69120
Universitatsklinikum Schleswig-Holstein
Kiel, 24105
Israel7 sites
Barzilai Medical Center
Ashkelon, 78278
Hadassah Medical Center PPDS -
Jerusalem, 91120
Rabin Medical Center - PPDS
Petah Tikva, 49100
The Chaim Sheba Medical Center - The Edmond and Lily Safra Children's Hospital
Ramat Gan, 52621
Kaplan Medical Center
Rehovot, 76100
ZIV Medical Center
Safed, 13100
Tel Aviv Sourasky Medical Center
Tel Aviv, Tel Aviv, 62431
Spain5 sites
Hospital Universitario A Coruña
A Coruña
Hospital Universitario Virgen de La Arrixaca
El Palmar, Murcia, 30120
Hospital Universitario Puerta de Hierro - Majadahonda
Madrid
Hospital Universitario Ramon y Cajal
Madrid
Hospital Universitario Virgen Macarena
Seville, 41009
France4 sites
CHRU Nantes
Nantes, Loire-Atlantique, 44805
Groupe Hospitalier Pitié Salpétrière
Paris, 75013
Hôpital Européen Georges Pompidou
Paris, 75015
Hôpital de Rangueil
Toulouse, 31403
Poland4 sites
Kardio Klinika Brynów
Katowice, Silesian Voivodeship
Collegium Medicum Uniwersytetu Jagiellonskiego
Krakow, Lesser Poland Voivodeship, 31-501
Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego
Poznan, 61-848
Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
Warsaw, 04-628
Belgium3 sites
Onze-Lieve-Vrouwziekenhuis
Aalst, Oost-Vlaanderen, 9300
Hôpital Erasme
Brussels, 1070
UZ Antwerpen
Edegem, Antwerpen, 2650
Denmark3 sites
Aarhus Universitetshospital
Aarhus N, 8200
Bispebjerg Hospital
København NV, 2400
Odense Universitetshospital
Odense, 5000
Czechia2 sites
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Institut Klinicke a Experimentalni Mediciny
Prague
Netherlands2 sites
Maastricht University Medical Center
Maastricht, Limburg, 6229 HX
Erasmus MC
Rotterdam, South Holland, 3015GD
Portugal2 sites
Hospital Garcia de Orta
Almada, 2805-267
Hospital da Luz
Lisbon, 1500-650
United Kingdom2 sites
University Hospital of Wales
Cardiff, South Glamergon, CF14 4XW
St Bartholomew's Hospital
London, W1G 8PH
About this study
Official title: A Randomized, Double Blind, Placebo Controlled Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten.
- Conditions
- Obstructive Hypertrophic Cardiomyopathy
- Being tested
- mavacamten, Placebo
- Keywords
- Symptomatic, left ventricular outflow tract gradient
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mavacamtenDrug
Also called MYK-461
mavacamten capsules
PlaceboDrug
placebo oral capsule
| Study group | Role | What they receive |
|---|---|---|
| mavacamten (MYK-461) | Experimental | Not described Receives: Drug: mavacamten |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 weeks
Secondary outcomes (5)
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.
Measured: 30 weeks
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.
Measured: 30 weeks
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.
Measured: 30 weeks
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.
Measured: 30 weeks
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.
Measured: 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2018
- Study start29 May 2018
- Primary completion14 Mar 2020
- Study completion6 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Obstructive Hypertrophic CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 251 participants (actual)
Sponsor and investigators
- Lead sponsor
- MyoKardia, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Information Team, Study director, MyoKardia, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03470545
- Sponsor's protocol ID
- MYK-461-005
- Acronym
- EXPLORER-HCM
- Status last verified
- May 2020
- First submitted
- 12 Mar 2018
- Last updated
- 4 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Olivotto I, Garcia-Pavia P, Tian Z, Owens AT, Lakdawala NK MD, Balaratnam G, Zhong Y, Memaj A, Barrett YC, Desai M. Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: An integrated analysis of phase 3 clinical trials. Am Heart J. 2026 Aug 24;303:107587. doi: 10.1016/j.ahj.2026.107587. Online ahead of print.
PubMed 42636950Saberi 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.
PubMed 42251960Wang A, Lakdawala NK, Abraham TP, Nilles EK, Wojdyla DM, Owens AT, Bach RG, Saberi S, Sehnert A, Cresci S. Association Between age or Duration of Diagnosis in Obstructive Hypertrophic Cardiomyopathy and Response to Mavacamten Treatment: Exploratory Analysis of the EXPLORER-HCM Trial. J Card Fail. 2025 Jun;31(6):901-911. doi: 10.1016/j.cardfail.2024.10.449. Epub 2024 Dec 7.
PubMed 39653325Arnold SV, Gosch KL, Dolan C, Fine JT, Masri A, Saberi S, Wang A, Elliott PM, Hegde SM, Lam J, Sehnert AJ, Cresci S, Bach RG, Spertus JA. Association of Echocardiographic Parameters and Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Nov 5;150(19):1560-1562. doi: 10.1161/CIRCULATIONAHA.123.067470. Epub 2024 Nov 4. No abstract available.
PubMed 39495835Sauer AJ, Sherrod CF, Gosch KL, Arnold SV, Reaney M, Zhong Y, Lam J, Wyrwich KW, Spertus JA. The Psychometric Performance of the Kansas City Cardiomyopathy Questionnaire-12 in Symptomatic Obstructive Hypertrophic Cardiomyopathy. J Card Fail. 2025 May;31(5):813-820. doi: 10.1016/j.cardfail.2024.09.010. Epub 2024 Sep 28.
PubMed 39349160Sherrod CF 4th, Spertus JA, Gosch KL, Wang A, Elliott PM, Lakdawala NK, Reaney M, Zhong Y, Lam J, Wyrwich KW, Sauer AJ. The Kansas City Cardiomyopathy Questionnaire in Relation to New York Heart Association Class. J Card Fail. 2025 Feb;31(2):481-484. doi: 10.1016/j.cardfail.2024.08.061. Epub 2024 Sep 28.
PubMed 39349158Garcia-Pavia P, Oreziak A, Masri A, Barriales-Villa R, Abraham TP, Owens AT, Jensen MK, Wojakowski W, Seidler T, Hagege A, Lakdawala NK, Wang A, Wheeler MT, Choudhury L, Balaratnam G, Shah A, Fox S, Hegde SM, Olivotto I. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. Eur Heart J. 2024 Dec 16;45(47):5071-5083. doi: 10.1093/eurheartj/ehae579.
PubMed 39217450Merali S, Salinger DH, Palmisano M, Sehnert AJ, Thanneer N, Back H, Seroogy JD, Gretler DD, Roy A, Perera V. Recommendation of mavacamten posology by model-based analyses in adults with obstructive hypertrophic cardiomyopathy. CPT Pharmacometrics Syst Pharmacol. 2024 Sep;13(9):1448-1461. doi: 10.1002/psp4.13138. Epub 2024 May 2.
PubMed 38695527Cresci S, Bach RG, Saberi S, Owens AT, Spertus JA, Hegde SM, Lakdawala NK, Nilles EK, Wojdyla DM, Sehnert AJ, Wang A. Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Feb 13;149(7):498-509. doi: 10.1161/CIRCULATIONAHA.123.065600. Epub 2023 Nov 14.
PubMed 37961906Wang A, Spertus JA, Wojdyla DM, Abraham TP, Nilles EK, Owens AT, Saberi S, Cresci S, Sehnert A, Lakdawala NK. Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial. JACC Heart Fail. 2024 Mar;12(3):567-579. doi: 10.1016/j.jchf.2023.07.030. Epub 2023 Oct 18.
PubMed 37855754Wheeler MT, Olivotto I, Elliott PM, Saberi S, Owens AT, Maurer MS, Masri A, Sehnert AJ, Edelberg JM, Chen YM, Florea V, Malhotra R, Wang A, Oreziak A, Myers J. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023 Mar 1;8(3):240-247. doi: 10.1001/jamacardio.2022.5099.
PubMed 36652223Nassif M, Fine JT, Dolan C, Reaney M, Addepalli P, Allen VD, Sehnert AJ, Gosch K, Spertus JA. Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy. JACC Heart Fail. 2022 Aug;10(8):531-539. doi: 10.1016/j.jchf.2022.03.002. Epub 2022 May 4.
PubMed 35902155Reaney M, Addepalli P, Allen V, Spertus JA, Dolan C, Sehnert AJ, Fine JT. Longitudinal Psychometric Analysis of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Using Outcomes from the Phase III EXPLORER-HCM Trial. Pharmacoecon Open. 2022 Jul;6(4):575-586. doi: 10.1007/s41669-022-00340-8. Epub 2022 Jun 20.
PubMed 35718845Hegde SM, Lester SJ, Solomon SD, Michels M, Elliott PM, Nagueh SF, Choudhury L, Zemanek D, Zwas DR, Jacoby D, Wang A, Ho CY, Li W, Sehnert AJ, Olivotto I, Abraham TP. Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2021 Dec 21;78(25):2518-2532. doi: 10.1016/j.jacc.2021.09.1381.
PubMed 34915982Xie J, Wang Y, Xu Y, Fine JT, Lam J, Garrison LP. Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial. J Med Econ. 2022 Jan-Dec;25(1):51-58. doi: 10.1080/13696998.2021.2011301.
PubMed 34907813
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo Controlled Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
- ClinicalTrials.gov ID
- NCT03470545
- Acronym / sponsor ID
- EXPLORER-HCM / MYK-461-005
- Conditions
- Obstructive Hypertrophic Cardiomyopathy
- Keywords
- Symptomatic, left ventricular outflow tract gradient
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 251 participants (actual)
- Lead sponsor
- MyoKardia, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 May 2018 (actual)
- Primary completion
- 14 Mar 2020 (actual)
- Study completion
- 6 May 2020 (actual)
- First posted
- 20 Mar 2018 (actual)
- Results
- Posted 4 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mavacamten (MYK-461) | Experimental | Drug: mavacamten |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mavacamtenAlso: MYK-461mavacamten capsules | Drug | mavacamten (MYK-461) |
| Placeboplacebo oral capsule | Drug | Placebo |
Primary outcome
Percentage of Participants Achieving A Clinical Response
Time frame: 30 weeks
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.
5 secondary outcomes
Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.
Time frame: 30 weeks
Change From Baseline to Week 30 in pVO2 as Assessed by CPET
Time frame: 30 weeks
Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30
Time frame: 30 weeks
Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score
Time frame: 30 weeks
Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score
Time frame: 30 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42636950Olivotto I, Garcia-Pavia P, Tian Z, Owens AT, Lakdawala NK MD, Balaratnam G, Zhong Y, Memaj A, Barrett YC, Desai M. Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: An integrated analysis of phase 3 clinical trials. Am Heart J. 2026 Aug 24;303:107587. doi: 10.1016/j.ahj.2026.107587. Online ahead of print.
- Derived from this study: PubMed 42251960Saberi 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.
- Derived from this study: PubMed 39653325Wang A, Lakdawala NK, Abraham TP, Nilles EK, Wojdyla DM, Owens AT, Bach RG, Saberi S, Sehnert A, Cresci S. Association Between age or Duration of Diagnosis in Obstructive Hypertrophic Cardiomyopathy and Response to Mavacamten Treatment: Exploratory Analysis of the EXPLORER-HCM Trial. J Card Fail. 2025 Jun;31(6):901-911. doi: 10.1016/j.cardfail.2024.10.449. Epub 2024 Dec 7.
- Derived from this study: PubMed 39495835Arnold SV, Gosch KL, Dolan C, Fine JT, Masri A, Saberi S, Wang A, Elliott PM, Hegde SM, Lam J, Sehnert AJ, Cresci S, Bach RG, Spertus JA. Association of Echocardiographic Parameters and Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Nov 5;150(19):1560-1562. doi: 10.1161/CIRCULATIONAHA.123.067470. Epub 2024 Nov 4. No abstract available.
- Derived from this study: PubMed 39349160Sauer AJ, Sherrod CF, Gosch KL, Arnold SV, Reaney M, Zhong Y, Lam J, Wyrwich KW, Spertus JA. The Psychometric Performance of the Kansas City Cardiomyopathy Questionnaire-12 in Symptomatic Obstructive Hypertrophic Cardiomyopathy. J Card Fail. 2025 May;31(5):813-820. doi: 10.1016/j.cardfail.2024.09.010. Epub 2024 Sep 28.
- Derived from this study: PubMed 39349158Sherrod CF 4th, Spertus JA, Gosch KL, Wang A, Elliott PM, Lakdawala NK, Reaney M, Zhong Y, Lam J, Wyrwich KW, Sauer AJ. The Kansas City Cardiomyopathy Questionnaire in Relation to New York Heart Association Class. J Card Fail. 2025 Feb;31(2):481-484. doi: 10.1016/j.cardfail.2024.08.061. Epub 2024 Sep 28.
- Derived from this study: PubMed 39217450Garcia-Pavia P, Oreziak A, Masri A, Barriales-Villa R, Abraham TP, Owens AT, Jensen MK, Wojakowski W, Seidler T, Hagege A, Lakdawala NK, Wang A, Wheeler MT, Choudhury L, Balaratnam G, Shah A, Fox S, Hegde SM, Olivotto I. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. Eur Heart J. 2024 Dec 16;45(47):5071-5083. doi: 10.1093/eurheartj/ehae579.
- Derived from this study: PubMed 38695527Merali S, Salinger DH, Palmisano M, Sehnert AJ, Thanneer N, Back H, Seroogy JD, Gretler DD, Roy A, Perera V. Recommendation of mavacamten posology by model-based analyses in adults with obstructive hypertrophic cardiomyopathy. CPT Pharmacometrics Syst Pharmacol. 2024 Sep;13(9):1448-1461. doi: 10.1002/psp4.13138. Epub 2024 May 2.
- Derived from this study: PubMed 37961906Cresci S, Bach RG, Saberi S, Owens AT, Spertus JA, Hegde SM, Lakdawala NK, Nilles EK, Wojdyla DM, Sehnert AJ, Wang A. Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Feb 13;149(7):498-509. doi: 10.1161/CIRCULATIONAHA.123.065600. Epub 2023 Nov 14.
- Derived from this study: PubMed 37855754Wang A, Spertus JA, Wojdyla DM, Abraham TP, Nilles EK, Owens AT, Saberi S, Cresci S, Sehnert A, Lakdawala NK. Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial. JACC Heart Fail. 2024 Mar;12(3):567-579. doi: 10.1016/j.jchf.2023.07.030. Epub 2023 Oct 18.
- Derived from this study: PubMed 36652223Wheeler MT, Olivotto I, Elliott PM, Saberi S, Owens AT, Maurer MS, Masri A, Sehnert AJ, Edelberg JM, Chen YM, Florea V, Malhotra R, Wang A, Oreziak A, Myers J. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023 Mar 1;8(3):240-247. doi: 10.1001/jamacardio.2022.5099.
- Derived from this study: PubMed 35902155Nassif M, Fine JT, Dolan C, Reaney M, Addepalli P, Allen VD, Sehnert AJ, Gosch K, Spertus JA. Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy. JACC Heart Fail. 2022 Aug;10(8):531-539. doi: 10.1016/j.jchf.2022.03.002. Epub 2022 May 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Information Team study director
MyoKardia, Inc.
71 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mavacamten in people with Obstructive Hypertrophic Cardiomyopathy, run by MyoKardia, Inc. at 71 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, Germany, Israel, Spain, France and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving A Clinical Response (time frame: 30 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03470545, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.