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

Primary Purpose

Cardiomyopathy, Hypertrophic Obstructive

Status
Active
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Mavacamten
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiomyopathy, Hypertrophic Obstructive focused on measuring Mavacamten, Obstructive Hypertrophic Cardiomyopathy (HCM)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Local Institution - 0020
  • Local Institution - 0026
  • Local Institution - 0016
  • Local Institution - 0017
  • Local Institution - 0023
  • Local Institution - 0019
  • Local Institution - 0015
  • Local Institution - 0028
  • Local Institution - 0027
  • Local Institution - 0011
  • Local Institution - 0014
  • Local Institution - 0012
  • Local Institution - 0010
  • Local Institution - 0009
  • Local Institution - 0003
  • Local Institution - 0001
  • Local Institution - 0007
  • Local Institution - 0005
  • Local Institution - 0013
  • Local Institution - 0018

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mavacamten

Arm Description

Outcomes

Primary Outcome Measures

Change from Baseline to Week 30 in post exercise left ventricular outflow tract (LVOT) peak gradient as determined by Doppler echocardiography

Secondary Outcome Measures

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.
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.
Change from baseline to Week 30 in N-terminal pro b-type natriuretic peptide (NT-proBNP)
Change from baseline to Week 30 in cardiac troponins

Full Information

First Posted
June 7, 2022
Last Updated
May 26, 2023
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT05414175
Brief Title
A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 19, 2022 (Actual)
Primary Completion Date
December 22, 2023 (Anticipated)
Study Completion Date
March 6, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiomyopathy, Hypertrophic Obstructive
Keywords
Mavacamten, Obstructive Hypertrophic Cardiomyopathy (HCM)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mavacamten
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Mavacamten
Other Intervention Name(s)
BMS-986427, MYK-461
Intervention Description
Specified dose on specified days
Primary Outcome Measure Information:
Title
Change from Baseline to Week 30 in post exercise left ventricular outflow tract (LVOT) peak gradient as determined by Doppler echocardiography
Time Frame
Up to Week 30
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 30 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS)
Description
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.
Time Frame
Up to Week 30
Title
Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) functional class from baseline to Week 30
Description
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.
Time Frame
Up to Week 30
Title
Change from baseline to Week 30 in N-terminal pro b-type natriuretic peptide (NT-proBNP)
Time Frame
Up to Week 30
Title
Change from baseline to Week 30 in cardiac troponins
Time Frame
Up to Week 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 0020
City
Uwajima
State/Province
Ehime
ZIP/Postal Code
798-8510
Country
Japan
Facility Name
Local Institution - 0026
City
Himeji-Shi
State/Province
Hyogo
ZIP/Postal Code
672-8044
Country
Japan
Facility Name
Local Institution - 0016
City
Kobe-shi
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Local Institution - 0017
City
Tsukuba-Shi
State/Province
Ibaraki
ZIP/Postal Code
305-0005
Country
Japan
Facility Name
Local Institution - 0023
City
Kanazawa-shi
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Local Institution - 0019
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
227-8501
Country
Japan
Facility Name
Local Institution - 0015
City
Nankoku-shi
State/Province
Kochi
ZIP/Postal Code
783-8505
Country
Japan
Facility Name
Local Institution - 0028
City
Tsu-Shi
State/Province
MIE
ZIP/Postal Code
514-0001
Country
Japan
Facility Name
Local Institution - 0027
City
Sendai-shi
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Local Institution - 0011
City
Suita-Shi
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Local Institution - 0014
City
Suita
State/Province
Osaka
ZIP/Postal Code
564-8565
Country
Japan
Facility Name
Local Institution - 0012
City
Hamamatsu-city
State/Province
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
Local Institution - 0010
City
Bunkyo-Ku
State/Province
Tokyo
ZIP/Postal Code
113-0033
Country
Japan
Facility Name
Local Institution - 0009
City
Chuo-Ku
State/Province
Tokyo
ZIP/Postal Code
104-0044
Country
Japan
Facility Name
Local Institution - 0003
City
Fuchu-Shi
State/Province
Tokyo
ZIP/Postal Code
1830003
Country
Japan
Facility Name
Local Institution - 0001
City
Itabashi-Ku
State/Province
Tokyo
ZIP/Postal Code
173-0003
Country
Japan
Facility Name
Local Institution - 0007
City
Koto-Ku
State/Province
Tokyo
ZIP/Postal Code
135-0061
Country
Japan
Facility Name
Local Institution - 0005
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
160-8582
Country
Japan
Facility Name
Local Institution - 0013
City
Shinjuku
State/Province
Tokyo
ZIP/Postal Code
1628666
Country
Japan
Facility Name
Local Institution - 0018
City
Osaka
ZIP/Postal Code
558-8558
Country
Japan

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
Investigator Inquiry Form

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A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

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