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The Purpose of This Study is to Compare the Efficacy and Safety of Aficamten (CK-3773274) Compared With Metoprolol Succinate in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction (MAPLE-HCM)

Primary Purpose

Obstructive Hypertrophic Cardiomyopathy (oHCM)

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)
Placebo to match aficamten
Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg)
Placebo to match metoprolol succinate
Sponsored by
Cytokinetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Hypertrophic Cardiomyopathy (oHCM) focused on measuring Obstructive Hypertrophic Cardiomyopathy, Aficamten, Metoprolol, oHCM, CK-3773274, CK-274, MAPLE-HCM, MAPLE, CY 6032

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants who meet all the following criteria at screening may be included in the trial: Males and females between 18 to 85 years of age, inclusive, at screening Body mass index < 35 kg/m2 Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography - Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory: ≥ 15 mm in one or more myocardial segments OR ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM NYHA class II or III Has a screening echocardiogram with the following determined by the echocardiography core laboratory: Resting LVOT-G > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND LVEF ≥ 60% Hemoglobin ≥ 10g/dL Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks Exclusion Criteria: Any of the following criteria will exclude potential participants from the trial: Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM History of intolerance or medical contraindication to beta blocker therapy Resting SBP of > 160 mmHg Resting heart rate of > 100 bpm Significant valvular heart disease Moderate-severe valvular aortic stenosis or fixed subaortic obstruction Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment) Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis) History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations) Documented room air oxygen saturation reading < 90% at screening Planned septal reduction treatment that cannot be deferred during the trial period History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed. Current or recent (< 4 weeks) therapy with disopyramide History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten

Sites / Locations

  • Alaska Heart and Vascular InstituteRecruiting
  • Mayo ClinicRecruiting
  • Cedars-Sinai Medical Center (Smidt Heart Institute)Recruiting
  • Yale New Haven HospitalRecruiting
  • Northwestern UniversityRecruiting
  • Massachusetts General HospitalRecruiting
  • Brigham and Women's HospitalRecruiting
  • Lahey Hospital & Medical CenterRecruiting
  • Saint Luke's Hospital of Kansas CityRecruiting
  • Morristown Medical CenterRecruiting
  • Oregon Health & Science UniversityRecruiting
  • Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Aficamten up to 20 mg plus placebo for metoprolol

Metoprolol succinate up to 200 mg plus placebo for aficamten

Arm Description

Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.

Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.

Outcomes

Primary Outcome Measures

Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM

Secondary Outcome Measures

Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class
Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification
Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)
Effect of aficamten compared with metoprolol succinate on patient health status
Change in left ventricular mass index (LVMI)
Effect of aficamten on mass of the heart as compared with metoprolol succinate
Change in left atrial volume index (LAVI)
Effect of aficamten on size of the heart as compared with metoprolol succinate
Change from baseline values in NT-proBNP from baseline to Week 24
Effect of CK-¬3773274 on NT-proBNP
Change in post-Valsalva LVOT-G from baseline to Week 24
Effect of aficamten on post-Valsalva LVOT-G

Full Information

First Posted
March 2, 2023
Last Updated
September 1, 2023
Sponsor
Cytokinetics
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1. Study Identification

Unique Protocol Identification Number
NCT05767346
Brief Title
The Purpose of This Study is to Compare the Efficacy and Safety of Aficamten (CK-3773274) Compared With Metoprolol Succinate in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
Acronym
MAPLE-HCM
Official Title
A Phase 3, Multi-center, Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2023 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Hypertrophic Cardiomyopathy (oHCM)
Keywords
Obstructive Hypertrophic Cardiomyopathy, Aficamten, Metoprolol, oHCM, CK-3773274, CK-274, MAPLE-HCM, MAPLE, CY 6032

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aficamten up to 20 mg plus placebo for metoprolol
Arm Type
Experimental
Arm Description
Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.
Arm Title
Metoprolol succinate up to 200 mg plus placebo for aficamten
Arm Type
Active Comparator
Arm Description
Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)
Intervention Description
Aficamten (CK-3773274) tablets administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo to match aficamten
Intervention Description
Placebo for aficamten (CK-3773274) administered orally
Intervention Type
Drug
Intervention Name(s)
Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg)
Intervention Description
Metoprolol succinate tablets administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo to match metoprolol succinate
Intervention Description
Placebo for metoprolol succinate administered orally
Primary Outcome Measure Information:
Title
Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
Description
Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class
Description
Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification
Time Frame
Baseline to Week 24
Title
Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)
Description
Effect of aficamten compared with metoprolol succinate on patient health status
Time Frame
Baseline to Week 24
Title
Change in left ventricular mass index (LVMI)
Description
Effect of aficamten on mass of the heart as compared with metoprolol succinate
Time Frame
Baseline to Week 24
Title
Change in left atrial volume index (LAVI)
Description
Effect of aficamten on size of the heart as compared with metoprolol succinate
Time Frame
Baseline to Week 24
Title
Change from baseline values in NT-proBNP from baseline to Week 24
Description
Effect of CK-¬3773274 on NT-proBNP
Time Frame
Baseline to Week 24
Title
Change in post-Valsalva LVOT-G from baseline to Week 24
Description
Effect of aficamten on post-Valsalva LVOT-G
Time Frame
Baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who meet all the following criteria at screening may be included in the trial: Males and females between 18 to 85 years of age, inclusive, at screening Body mass index < 35 kg/m2 Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography - Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory: ≥ 15 mm in one or more myocardial segments OR ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM NYHA class II or III Has a screening echocardiogram with the following determined by the echocardiography core laboratory: Resting LVOT-G > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND LVEF ≥ 60% Hemoglobin ≥ 10g/dL Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks Exclusion Criteria: Any of the following criteria will exclude potential participants from the trial: Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM History of intolerance or medical contraindication to beta blocker therapy Resting SBP of > 160 mmHg Resting heart rate of > 100 bpm Significant valvular heart disease Moderate-severe valvular aortic stenosis or fixed subaortic obstruction Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment) Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis) History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations) Documented room air oxygen saturation reading < 90% at screening Planned septal reduction treatment that cannot be deferred during the trial period History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed. Current or recent (< 4 weeks) therapy with disopyramide History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cytokinetics MD
Phone
650-624-2929
Email
medicalaffairs@cytokinetics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scientific Leadership
Organizational Affiliation
Cytokinetics
Official's Role
Study Director
Facility Information:
Facility Name
Alaska Heart and Vascular Institute
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Name
Cedars-Sinai Medical Center (Smidt Heart Institute)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwestern University
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Individual Site Status
Recruiting
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Lahey Hospital & Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01803
Country
United States
Individual Site Status
Recruiting
Facility Name
Saint Luke's Hospital of Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Individual Site Status
Recruiting
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Individual Site Status
Recruiting
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Name
Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

The Purpose of This Study is to Compare the Efficacy and Safety of Aficamten (CK-3773274) Compared With Metoprolol Succinate in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

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