A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Cardiomyopathy, Hypertrophic Obstructive Clinical Trial

— HORIZON-HCM  

Official title:

A Phase 3, Open-label, Single Arm, Clinical Study to Evaluate Efficacy, Safety and Tolerability of Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05414175
• Other study ID #: CV027-004
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 19, 2022
• Est. completion date: March 6, 2026

Study information

• Verified date: December 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness, safety, and tolerability of a 30-week course of mavacamten and the long-term effects of mavacamten in Japanese participants with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 38
• Est. completion date: March 6, 2026
• Est. primary completion date: November 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 and greater, body weight = 35kg
• Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs)
• Diagnosed with obstructive hypertrophic cardiomyopathy consistent with current American College of Cardiology Foundation/American Heart Association, European Society of Cardiology, and Japanese Circulation Society guidelines
• Has documented left ventricular ejection fraction (LVEF) =60% NYHA Class II or III

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 atrial fibrillation with atrial fibrillation present at the time of 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 cibenzoline, disopyramide or ranolazine
• Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of beta blockers and verapamil or a combination of beta blockers and diltiazem
• 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 Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Cardiomyopathy, Hypertrophic Obstructive
• Hypertrophy

Intervention

Drug:
• Mavacamten
Specified dose on specified days

Locations

Country	Name	City	State
Japan	Local Institution - 0010	Bunkyo-Ku	Tokyo
Japan	Local Institution - 0009	Chuo-Ku	Tokyo
Japan	Local Institution - 0003	Fuchu-Shi	Tokyo
Japan	Local Institution - 0012	Hamamatsu-city	Shizuoka
Japan	Local Institution - 0026	Himeji-Shi	Hyogo
Japan	Local Institution - 0001	Itabashi-Ku	Tokyo
Japan	Local Institution - 0023	Kanazawa-shi	Ishikawa
Japan	Local Institution - 0016	Kobe-shi	Hyogo
Japan	Local Institution - 0007	Koto-Ku	Tokyo
Japan	Local Institution - 0015	Nankoku-shi	Kochi
Japan	Local Institution - 0018	Osaka
Japan	Local Institution - 0027	Sendai	Miyagi
Japan	Local Institution - 0013	Shinjuku	Tokyo
Japan	Local Institution - 0005	Shinjuku-Ku	Tokyo
Japan	Local Institution - 0014	Suita	Osaka
Japan	Local Institution - 0011	Suita-Shi	Osaka
Japan	Local Institution - 0028	Tsu-Shi	MIE
Japan	Local Institution - 0017	Tsukuba-Shi	Ibaraki
Japan	Local Institution - 0020	Uwajima	Ehime
Japan	Local Institution - 0019	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 30 in post exercise left ventricular outflow tract (LVOT) peak gradient as determined by Doppler echocardiography		Up to Week 30
Secondary	Change from Baseline to Week 30 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS)	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. 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 score (KCCQ-CSS) combines the physical limitation and total symptom scores.	Up to Week 30
Secondary	Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) functional class from baseline to Week 30	The New York Heart Association (NYHA) functional classification of heart failure assigns participants to 1 of 4 categories based on the participant's symptoms. Heart failure classification will be assessed by the Investigator at specified timepoints in the study. NYHA class at Week 30 will be compared to baseline and the proportion of participants with an improvement of at least one class will be determined.	Up to Week 30
Secondary	Change from baseline to Week 30 in N-terminal pro b-type natriuretic peptide (NT-proBNP)		Up to Week 30
Secondary	Change from baseline to Week 30 in cardiac troponins		Up to Week 30

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls