A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy (HORIZON-HCM)

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

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).

Study Overview

• Status: Completed
• Conditions: Cardiomyopathy, Hypertrophic Obstructive
• Intervention / Treatment: Drug: Mavacamten

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 558-8558
    • Local Institution - 0018
  • Ehime
    • Uwajima, Ehime, Japan, 798-8510
      • Local Institution - 0020
  • Hyōgo
    • Himeji-Shi, Hyōgo, Japan, 672-8044
      • Local Institution - 0026
    • Kobe, Hyōgo, Japan, 650-0047
      • Local Institution - 0016
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-0005
      • Local Institution - 0017
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Local Institution - 0023
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 227-8501
      • Local Institution - 0019
  • Kochi
    • Nankoku-shi, Kochi, Japan, 783-8505
      • Local Institution - 0015
  • Mie-ken
    • Tsu, Mie-ken, Japan, 514-8507
      • Local Institution - 0028
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Local Institution - 0027
  • Osaka
    • Suita, Osaka, Japan, 564-8565
      • Local Institution - 0014
    • Suita-Shi, Osaka, Japan, 565-0871
      • Local Institution - 0011
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Local Institution - 0012
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-0033
      • Local Institution - 0010
    • Chuo-Ku, Tokyo, Japan, 104-0044
      • Local Institution - 0009
    • Fuchu-Shi, Tokyo, Japan, 1830003
      • Local Institution - 0003
    • Itabashi-Ku, Tokyo, Japan, 173-0003
      • Local Institution - 0001
    • Koto-Ku, Tokyo, Japan, 135-0061
      • Local Institution - 0007
    • Shinjuku-Ku, Tokyo, Japan, 160-8582
      • Local Institution - 0005
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Local Institution - 0013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mavacamten	Drug: Mavacamten; Specified dose on specified days; Other Names: BMS-986427; MYK-461

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30	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 doppler echocardiography. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.	At Baseline and Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30	The KCCQ-23 is a 23-item, self-administered questionnaire that measures the impact of a participant's cardiovascular disease or its treatment on 6 distinct domains using a 2-week recall period: symptoms/signs, physical limitation, quality of life (QoL), social limitations, self-efficacy, and symptom stability. The KCCQ 23 Clinical Summary Score (CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ 23. The CSS, TSS, and the PL score range from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations. The CSS is a mean of the TSS and the PL score. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.	At Baseline and Week 30
Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30	The NYHA Functional Classification of Heart Failure (HF) assigns participants to 1 of 4 categories based on the participant's symptoms. Class I (No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea); Class II (Slight limitation of physical activity, Comfortable at rest, Ordinary physical activity results in fatigue, palpitation, dyspnea); Class III (Marked limitation of physical activity, Comfortable at rest, Less-than ordinary-activity causes fatigue, palpitation, or dyspnea) and Class IV (Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases). Improvement is defined as participant moving to lower class category from a higher one. Baseline is defined as last non-missing measurement prior to the first dose.	Baseline and at Week 30
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30	Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose.	At baseline and week 30
Change From Baseline in Cardiac Troponin I at Week 30	Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.	At baseline and week 30
Change From Baseline in Cardiac Troponin T at Week 30	Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.	At baseline and week 30

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2022
• Primary Completion (Actual): November 27, 2023
• Study Completion (Actual): December 11, 2025

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Mavacamten; Obstructive Hypertrophic Cardiomyopathy (HCM)
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; MYK-461
• Other Study ID Numbers: CV027-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes