A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive HCM)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated in the real-world setting. The registry study also provide a real-world understanding of the current obstructive HCM patient population, treatment patterns, and clinical relevant outcomes for patients with symptomatic obstructive HCM in the US.

Official Title
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Deliver Insights in Hypertrophic Cardiomyopathy and Observational Outcomes in Real World: United States Prospective Registry Study

Conditions
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Obstructive Hypertrophic Cardiomyopathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent form (ICF) and any required privacy authorization prior to the initiation of study procedures. i. Diagnosis of obstructive HCM consistent with 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines. ii. Obstructive HCM is defined clinically by the presence of increased LV wall thickness ≥ 15 mm (or ≥ 13 mm with positive family history of HCM) in a nondilated ventricular chamber that is not solely explained by abnormal loading conditions (eg, another cardiac or systemic disease) and peak LVOT gradient of ≥ 30 mmHg at rest or with provocation. Has documented LVEF of ≥ 55% recorded by echocardiography within the last 6 months. Symptoms consistent with NYHA functional class II-IV. ≥ 18 years of age at the time of informed consent. Receiving BBs, non-dihydropyridine calcium. channel blockers (non-DHP CCBs), disopyramide, and/or mavacamten (once available) as part of routine clinical care; or currently receiving no treatment due to intolerance or failure of prior treatment (eg, BBs, non-DHP CCBs, or disopyramide) for obstructive HCM. Exclusion Criteria: Known phenocopy disease (eg, Fabry disease, amyloidosis) or LV hypertrophy associated with hypertension. Documentation of any fixed obstruction of the outflow tract such as aortic valve stenosis or replacement. Prior treatment of obstructive HCM with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) within 6 months prior to enrollment; participants with an unsuccessful myectomy or percutaneous ASA performed > 6 months prior to enrollment may be enrolled. Naïve to treatment for obstructive HCM (ie, never treated with BBs, non-DHP CCBs, or disopyramide). Receiving an investigational therapeutic agent for obstructive HCM (eg, myosin-inhibitors other than mavacamten) in an interventional clinical trial at participant enrollment. Previously or currently enrolled in a long-term safety extension study of mavacamten (eg, EXPLORER-HCM [ClinicalTrials.gov, NCT03470545], MAVA-LTE [NCT03723655], PIONEER-OLE [NCT03496168], VALORHCM [NCT04349072], or MAVERICK [NCT03442764])

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mavacamten<br>Participants will receive mavacamten as prescribed by a physician according to standard of care for symptomatic oHCM | |
| Beta-blocker (BB) / non-dihydropyridine (non-DHP) calcium channel blocker (CCB) / disopyramide<br>Participants will receive BB/non-DHP CCB/disopyramide as prescribed by a physician according to standard of care for symptomatic oHCM | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of new or worsening heart failure due to systolic dysfunction among participants with symptomatic obstructive HCM during periods of exposure to mavacamten and other oHCM treatment | Systolic dysfunction defined as symptomatic Left Ventricular Ejection Fraction (LVEF) < 50% | Up to 5 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of arrhythmia | Incidence rates of participants with arrhythmia (new onset) | Up to 5 Years | 
| Occurrence of Major Adverse Cardiovascular Events (MACE) | A composite endpoint consisting of non-fatal acute Myocardial Infarction (MI), stroke, hospitalization due to Heart Failure (HF) and Cardiovascular (CV) mortality | Up to 5 Years | 
| Occurrence of non-fatal acute Myocardial Infarction (MI) |  | Up to 5 Years | 
| Occurrence of Stroke |  | Up to 5 Years | 
| Occurrence of hospitalization due to heart failure |  | Up to 5 Years | 
| Occurrence of cardiovascular mortality |  | Up to 5 Years | 
| Occurrence of all-cause mortality |  | Up to 5 Years | 
| Evaluation of functional responses: New York Heart Association (NYHA) function class | Percentage of Participants Whose NYHA Class Changes | Up to 5 Years | 
| Evaluation of functional responses: Left Ventricular Outflow Tract (LVOT) gradient | Mean Change From Baseline in LVOT Gradients At Rest and Provoked | Baseline, 5 Years | 
| Evaluation of functional responses: LVEF | Mean Change from Baseline in LVEF | Baseline, 5 Years | 
| Evaluation of patient reported outcome measure: Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23) | The KCCQ-23 is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. | Baseline, 5 Years | 
| Evaluation of patient reported outcome measure: EuroQol Five Dimensions Questionnaire (5-level) (EQ-5D-5L): Health Utility Index | The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L health utility index and EQ Visual Analog Scale (VAS). EQ-5D-5L health utility index is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participants select an answer for each of the 5 dimensions that best matches his/her health today. Responses are used to generate a weighted summary index, which ranges from 0 to 1.00. A higher score indicates better health and positive changes from baseline indicate improvement of health. | Baseline, 5 Years | 
| Evaluation of patient reported outcome measure: EQ-5D-5L: VAS | The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and VAS. The VAS self-rating records the participant's own assessment of his or her overall health status at the time of completion, on a vertical line VAS with scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). A higher score indicates better health and positive changes from baseline indicate improvement of health status. | Baseline, 5 Years | 
| Evaluation of biomarkers of response: NT-proBNP | Change From Baseline in Serum concentration of NT-proBNP | Baseline, 5 Years | 
| Evaluation of biomarkers of response: Cardiac troponin | Change From Baseline in Serum Concentration of Cardiac Troponins | Baseline, 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obstructive hypertrophic cardiomyopathy, Obstructive HCM (oHCM), Mavacamten, Heart failure, oHCM