Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM)

September 7, 2021 updated by: MyoKardia, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
251

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1070
        • Hôpital Erasme
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • UZ Antwerpen
    • Oost-Vlaanderen
      • Aalst, Oost-Vlaanderen, Belgium, 9300
        • Onze-Lieve-Vrouwziekenhuis
  • Czechia
      • Prague, Czechia
        • Institut Klinicke a Experimentalni Mediciny
      • Praha 2, Czechia, 128 08
        • Vseobecna Fakultni Nemocnice V Praze
  • Denmark
      • Aarhus N, Denmark, 8200
        • Aarhus Universitetshospital
      • København NV, Denmark, 2400
        • Bispebjerg Hospital
      • Odense, Denmark, 5000
        • Odense Universitetshospital
  • France
      • Paris, France, 75015
        • Hôpital Européen Georges Pompidou
      • Paris, France, 75013
        • Groupe Hospitalier Pitié Salpêtrière
      • Toulouse, France, 31403
        • Hopital de Rangueil
    • Loire-Atlantique
      • Nantes, Loire-Atlantique, France, 44805
        • CHRU Nantes
  • Germany
      • Bad Nauheim, Germany, 61231
        • Kerckhoff-Klinik-Forschungs-GmbH
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin
      • Berlin, Germany, 13125
        • Charité Campus Buch - Experimental and Clinical Research Center
      • Dresden, Germany, 01277
        • Cardiologicum Dresden und Pirna
      • Heidelberg, Germany, 69120
        • University Clinic Heidelberg - PPDS
      • Kiel, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein
    • Neidersachsen
      • Göttingen, Neidersachsen, Germany
        • University Medicine Gottingen
  • Israel
      • Ashkelon, Israel, 78278
        • Barzilai Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center PPDS -
      • Petach Tikva, Israel, 49100
        • Rabin Medical Center - PPDS
      • Ramat-Gan, Israel, 52621
        • The Chaim Sheba Medical Center - The Edmond and Lily Safra Children's Hospital
      • Reẖovot, Israel, 76100
        • Kaplan Medical Center
      • Safed, Israel, 13100
        • Ziv Medical Center
    • Tel-Aviv
      • Tel Aviv, Tel-Aviv, Israel, 62431
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Firenze, Italy
        • Azienda Ospedaliera Universitaria Careggi
  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Maastricht University Medical Center
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015GD
        • Erasmus MC
  • Poland
      • Poznań, Poland, 61-848
        • Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego
      • Warsaw, Poland, 04-628
        • Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
    • Malopolskie
      • Kraków, Malopolskie, Poland, 31-501
        • Collegium Medicum Uniwersytetu Jagiellonskiego
    • Slaskie
      • Katowice, Slaskie, Poland
        • Kardio Klinika Brynow
  • Portugal
      • Almada, Portugal, 2805-267
        • Hospital Garcia de Orta
      • Lisboa, Portugal, 1500-650
        • Hospital da Luz
  • Spain
      • La Coruña, Spain
        • Hospital Universitario A Coruna
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Hospital Universitario Puerta de Hierro - Majadahonda
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Universitario Virgen de la Arrixaca
  • United Kingdom
      • London, United Kingdom, W1G 8PH
        • St Bartholomew's Hospital
    • South Glamergon
      • Cardiff, South Glamergon, United Kingdom, CF14 4XW
        • University Hospital of wales
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Arizona
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center (Smidt Heart Institute)
      • San Francisco, California, United States, 94143
        • UCSF School of Medicine
      • Stanford, California, United States, 94305
        • Stanford University
    • Connecticut
      • New Haven, Connecticut, United States, 16511
        • Yale New Haven Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Jacksonville - PPDS
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Grand Rapids, Michigan, United States, 49512
        • Spectrum Health
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10017
        • NYU Langone Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke Cardiology at Southpoint
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18018
        • St. Luke's Cardiology Associates
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania (Penn Heart and Vascular Center)
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center Presbyterian
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • Methodist University Hospital
    • Texas
      • Dallas, Texas, United States, 75235
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • University of Texas Houston Medical School
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
      • Salt Lake City, Utah, United States, 84107
        • Intermountain Medical Center
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
placebo oral capsule
Experimental: mavacamten (MYK-461)
Drug: mavacamten
mavacamten capsules
Other Names:
  • MYK-461

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
30 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.
Time Frame: 30 weeks
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.
30 weeks
Change From Baseline to Week 30 in pVO2 as Assessed by CPET
Time Frame: 30 weeks
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.
30 weeks
Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30
Time Frame: 30 weeks
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.
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
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.
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
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.
30 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MyoKardia, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Information Team, MyoKardia, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 14, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 6, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 12, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MYK-461-005

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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