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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03470545
Other study ID # MYK-461-005
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date May 29, 2018
Est. completion date May 6, 2020

Study information

Verified date May 2020
Source MyoKardia, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


Recruitment information / eligibility

Status Completed
Enrollment 251
Est. completion date May 6, 2020
Est. primary completion date March 14, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 ß-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


Related Conditions & MeSH terms


Intervention

Drug:
mavacamten
mavacamten capsules
Placebo
placebo oral capsule

Locations

Country Name City State
Belgium Onze-Lieve-Vrouwziekenhuis Aalst Oost-Vlaanderen
Belgium Hôpital Erasme Brussels
Belgium UZ Antwerpen Edegem Antwerpen
Czechia Institut Klinicke a Experimentalni Mediciny Prague
Czechia Vseobecna fakultni nemocnice v Praze Praha 2
Denmark Aarhus Universitetshospital Aarhus N
Denmark Bispebjerg Hospital København NV
Denmark Odense Universitetshospital Odense
France CHRU Nantes Nantes Loire-Atlantique
France Groupe Hospitalier Pitié Salpétrière Paris
France Hôpital Européen Georges Pompidou Paris
France Hôpital de Rangueil Toulouse
Germany Kerckhoff-Klinik-Forschungs-GmbH Bad Nauheim
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Charité Campus Buch - Experimental and Clinical Research Center Berlin
Germany Cardiologicum Dresden und Pirna Dresden
Germany University Medicine Göttingen Göttingen Neidersachsen
Germany University Clinic Heidelberg - PPDS Heidelberg
Germany Universitatsklinikum Schleswig-Holstein Kiel
Israel Barzilai Medical Center Ashkelon
Israel Hadassah Medical Center PPDS - Jerusalem
Israel Rabin Medical Center - PPDS Petach Tikva
Israel The Chaim Sheba Medical Center - The Edmond and Lily Safra Children's Hospital Ramat-Gan
Israel Kaplan Medical Center Re?ovot
Israel ZIV Medical Center Safed
Israel Tel Aviv Sourasky Medical Center Tel Aviv Tel-Aviv
Italy Azienda Ospedaliera Universitaria Careggi Firenze
Netherlands Maastricht University Medical Center Maastricht Limburg
Netherlands Erasmus MC Rotterdam Zuid-Holland
Poland Kardio Klinika Brynów Katowice Slaskie
Poland Collegium Medicum Uniwersytetu Jagiellonskiego Kraków Malopolskie
Poland Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego Poznan
Poland Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego Warsaw
Portugal Hospital Garcia de Orta Almada
Portugal Hospital da Luz Lisboa
Spain Hospital Universitario Virgen de La Arrixaca El Palmar Murcia
Spain Hospital Universitario A Coruña La Coruña
Spain Hospital Universitario Puerta de Hierro - Majadahonda Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Hospital Universitario Virgen Macarena Sevilla
United Kingdom University Hospital of Wales Cardiff South Glamergon
United Kingdom St Bartholomew's Hospital London
United States University of Michigan Ann Arbor Michigan
United States St. Luke's Cardiology Associates Bethlehem Pennsylvania
United States Brigham and Women's Hospital Boston Massachusetts
United States Carolinas Medical Center Charlotte North Carolina
United States University of Virginia Health System Charlottesville Virginia
United States Northwestern University Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States University of Texas Southwestern Medical Center Dallas Texas
United States Duke Cardiology at Southpoint Durham North Carolina
United States Spectrum Health Grand Rapids Michigan
United States Houston Methodist Hospital Houston Texas
United States University of Texas Houston Medical School Houston Texas
United States University Of Iowa Hospitals And Clinics Iowa City Iowa
United States Mayo Clinic Jacksonville - PPDS Jacksonville Florida
United States Cedars-Sinai Medical Center (Smidt Heart Institute) Los Angeles California
United States Methodist University Hospital Memphis Tennessee
United States Yale New Haven Hospital New Haven Connecticut
United States Columbia University Medical Center New York New York
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 Oregon Health & Science University Portland Oregon
United States Washington University School of Medicine Saint Louis Missouri
United States Intermountain Medical Center Salt Lake City Utah
United States University of Utah Salt Lake City Utah
United States UCSF School of Medicine San Francisco California
United States Mayo Clinic Arizona Scottsdale Arizona
United States University of Washington Medical Center Seattle Washington
United States Stanford University Stanford California

Sponsors (1)

Lead Sponsor Collaborator
MyoKardia, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
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. 30 weeks
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. 30 weeks
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. 30 weeks
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. 30 weeks
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. 30 weeks
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. 30 weeks
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