A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)

Non-obstructive Hypertrophic Cardiomyopathy Clinical Trial

— MAVERICK-HCM  

Official title:

A Randomized, Double-blind, Placebo-controlled, Concentration-guided, Exploratory Study of Mavacameten in Patients With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM) and Preserved Left Ventricular Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03442764
• Other study ID #: MYK-461-006
• Status: Completed
• Phase: Phase 2
• Start date: March 30, 2018
• Est. completion date: January 7, 2020

Study information

• Verified date: July 2022
• Source: MyoKardia, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, exploratory, randomized, double-blind study of the administration of mavacamten in 60 participants with symptomatic nHCM randomized to receive a 16-week course of mavacamten doses titrated to achieve 1 of 2 target drug concentrations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: January 7, 2020
• Est. primary completion date: January 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Diagnosed with nHCM (hypertrophied and non-dilated left ventricle in absence of systemic or other known cause), with LV wall thickness = 15mm at Screening or = 13mm with a positive family history of HCM.

• Age 18 and greater, Body weight > 45kg

• Documented LVEF = 55% at the Screening as determined by echo central lab

• LVOT gradient < 30 mmHg at rest AND during Valsalva AND post-exercise

• NYHA functional class II or III

• Elevated NT-proBNP at rest

Key Exclusion Criteria:

• History of syncope, sustained ventricular tachyarrhythmia with exercise, obstructive coronary artery disease or myocardial infarction within the past 6 months

• History of resuscitated sudden cardiac arrest at any time or known appropriate implantable cardioverter defibrillator (ICD) discharge within 6 months prior to Screening

• Current treatment with disopyramide or ranolazine (within 14 days prior to Screening)

• Current or planned treatment during the study with a combination of beta-blockers and calcium channel blockers

• Has been treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) within 6 months prior to Screening

• History of resting or post-exercise LVOT >30 mmHg unless subsequently treated by septal reduction

• Has QTc Fridericia (QTcF) >480 ms or any other ECG abnormality considered by the investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type II)

• Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate-controlled within 1 year of Screening

• History of clinically significant malignant disease within 10 years such as non-metastatic cutaneous squamous cell or basal cell carcinoma

• History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or MyoKardia physician, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophy
• Non-obstructive Hypertrophic Cardiomyopathy

Intervention

Drug:
• mavacamten
MYK-461
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Michigan Medicine	Ann Arbor	Michigan
United States	University of Maryland Medical System	Baltimore	Maryland
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	Charlottesville	Virginia
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	The University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke Cardiology at Southpoint	Durham	North Carolina
United States	Northwestern University	Evanston	Illinois
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor St. Luke Medical Center at Houston, Texas Heart Institute Out-patient Clinic	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	St. Vincent Medical Group	Indianapolis	Indiana
United States	University of Iowa Hospitals and clinics	Iowa City	Iowa
United States	Cedars-Sinai Medical Center (Smidt Heart Institute)	Los Angeles	California
United States	Unity Point Health Meriter Heart and Vascular Institute	Madison	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Intermountain Medical Center	Murray	Utah
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	NYU Langone Medical Center	New York	New York
United States	Stanford Hospital and Clinics/Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
MyoKardia, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE)	This is the percentage of participants who experienced at least one treatment emergent adverse event (TEAE)	From first dose to 8 weeks following last dose (Up to 24 weeks)
Primary	Percentage of Participants Who Experienced at Least One Serious Treatment-emergent Adverse Event (STEAE)	This is the percentage of participants who experienced at least one serious treatment-emergent adverse event (STEAE)	From first dose to 8 weeks following last dose (Up to 24 weeks)

External Links

•   PUBLICATION: Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy