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

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

251

Phase

  • 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 Pitie Salpetriere
      • Toulouse, France, 31403
        • Hôpital 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 Göttingen
  • 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 Coruña
      • 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

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
Intervention / Treatment
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

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

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

MyoKardia, Inc.

Investigators

  • 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)

May 29, 2018

Primary Completion (Actual)

March 14, 2020

Study Completion (Actual)

May 6, 2020

Study Registration Dates

First Submitted

March 12, 2018

First Submitted That Met QC Criteria

March 17, 2018

First Posted (Actual)

March 20, 2018

Study Record Updates

Last Update Posted (Actual)

October 4, 2021

Last Update Submitted That Met QC Criteria

September 7, 2021

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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