Clinical trial NCT03442764: A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-obstructive Hypertrophic Cardiomyopathy
Lead sponsor: MyoKardia, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-22
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: From first dose to 8 weeks following last dose (Up to 24 weeks)
measure: Percentage of Participants Who Experienced at Least One Serious Treatment-emergent Adverse Event (STEAE)
timeFrame: From first dose to 8 weeks following last dose (Up to 24 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Smidt Heart Institute)
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics/Stanford University
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Medical Group
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Medical System
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke Cardiology at Southpoint
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Cardiology Associates
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke Medical Center at Houston, Texas Heart Institute Out-patient Clinic
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: Unity Point Health Meriter Heart and Vascular Institute
state: Wisconsin
Study officials:
affiliation: MyoKardia, Inc.
name: Myokardia Medical Information Team
role: STUDY_DIRECTOR
References:
citation: Ho CY, Mealiffe ME, Bach RG, Bhattacharya M, Choudhury L, Edelberg JM, Hegde SM, Jacoby D, Lakdawala NK, Lester SJ, Ma Y, Marian AJ, Nagueh SF, Owens A, Rader F, Saberi S, Sehnert AJ, Sherrid MV, Solomon SD, Wang A, Wever-Pinzon O, Wong TC, Heitner SB. Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2020 Jun 2;75(21):2649-2660. doi: 10.1016/j.jacc.2020.03.064.