Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
- Conditions
- Obstructive Hypertrophic Cardiomyopathy
- Interventions
- Drug: PlaceboDrug: mavacamten
- Registration Number
- NCT03470545
- Lead Sponsor
- MyoKardia, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 251
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - mavacamten (MYK-461) mavacamten -
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving A Clinical Response 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.
- Secondary Outcome Measures
Name Time Method Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient. 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.
Change From Baseline to Week 30 in pVO2 as Assessed by CPET 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.
Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30 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.
Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score 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.
Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score 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.
Trial Locations
- Locations (71)
Cedars-Sinai Medical Center (Smidt Heart Institute)
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas Houston Medical School
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
UCSF School of Medicine
🇺🇸San Francisco, California, United States
Duke Cardiology at Southpoint
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Intermountain Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic Jacksonville - PPDS
🇺🇸Jacksonville, Florida, United States
Charité Campus Buch - Experimental and Clinical Research Center
🇩🇪Berlin, Germany
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
University Clinic Heidelberg - PPDS
🇩🇪Heidelberg, Germany
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University Of Iowa Hospitals And Clinics
🇺🇸Iowa City, Iowa, United States
St. Luke's Cardiology Associates
🇺🇸Bethlehem, Pennsylvania, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Hôpital de Rangueil
🇫🇷Toulouse, France
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Onze-Lieve-Vrouwziekenhuis
🇧🇪Aalst, Oost-Vlaanderen, Belgium
ZIV Medical Center
🇮🇱Safed, Israel
Kerckhoff-Klinik-Forschungs-GmbH
🇩🇪Bad Nauheim, Germany
Hospital da Luz
🇵🇹Lisboa, Portugal
Odense Universitetshospital
🇩🇰Odense, Denmark
Cardiologicum Dresden und Pirna
🇩🇪Dresden, Germany
Institut Klinicke a Experimentalni Mediciny
🇨🇿Prague, Czechia
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Tel-Aviv, Israel
University Medicine Göttingen
🇩🇪Göttingen, Neidersachsen, Germany
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Erasmus MC
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Kardio Klinika Brynów
🇵🇱Katowice, Slaskie, Poland
University Hospital of Wales
🇬🇧Cardiff, South Glamergon, United Kingdom
Hospital Universitario A Coruña
🇪🇸La Coruña, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Bispebjerg Hospital
🇩🇰København NV, Denmark
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
CHRU Nantes
🇫🇷Nantes, Loire-Atlantique, France
Maastricht University Medical Center
🇳🇱Maastricht, Limburg, Netherlands
Hôpital Erasme
🇧🇪Brussels, Belgium
Collegium Medicum Uniwersytetu Jagiellonskiego
🇵🇱Kraków, Malopolskie, Poland
Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
🇵🇱Warsaw, Poland
Hospital Garcia de Orta
🇵🇹Almada, Portugal
Hospital Universitario Virgen de La Arrixaca
🇪🇸El Palmar, Murcia, Spain
Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznań, Poland
Rabin Medical Center - PPDS
🇮🇱Petach Tikva, Israel
Columbia University Medical Center
🇺🇸New York, New York, United States
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
Groupe Hospitalier Pitié Salpétrière
🇫🇷Paris, France
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Spain
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Stanford University
🇺🇸Stanford, California, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
University of Pennsylvania (Penn Heart and Vascular Center)
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Presbyterian
🇺🇸Pittsburgh, Pennsylvania, United States
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Hadassah Medical Center PPDS -
🇮🇱Jerusalem, Israel
The Chaim Sheba Medical Center - The Edmond and Lily Safra Children's Hospital
🇮🇱Ramat-Gan, Israel
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States