A Study to Evaluate Mavacamten Impact on Myocardial Structure in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the mavacamten impact on myocardial structure with cardiac magnetic resonance imaging (CMR) in adult participants with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) [New York Heart Association (NYHA) Functional Class II or III].

Official Title
-----------------
MEMENTO - A Phase 3b/4, Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy to Assess the Impact on Myocardial Structure With Cardiac Magnetic Resonance Imaging (CMR)

Conditions
-----------------
Cardiomyopathy, Hypertrophic

Intervention / Treatment
-----------------
* Drug: Mavacamten
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with obstructive hypertrophic cardiomyopathy (oHCM), in accordance with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines as below: Left ventricular outflow tract (LVOT) peak gradient ≥ 30 mm Hg and ≥ 50 mm Hg after Valsalva or after exercise Left ventricular ejection fraction (LVEF) ≥ 55% at rest New York Heart Association (NYHA) functional class II or III symptoms Exclusion Criteria: A known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM Documented obstructive coronary artery disease or history of myocardial infarction A history of resuscitated sudden cardiac arrest or life-threatening ventricular arrhythmia within 6 months prior to screening An implantable cardioverter defibrillator (ICD) or pacemaker, or another contraindication for cardiac magnetic resonance imaging (CMR) Note: Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavacamten<br> | Drug: Mavacamten<br>* Specified dose on specified days<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of left atrial volume index (LAVI) and left ventricular mass index (LVMI) at Week 48 | Participants achieving both of the following criteria at Week 48 cardiac magnetic resonance imaging (CMR) assessment: A decrease of at least 5 mL/m2 in LAVI from baseline A decrease of at least 5 g/m2 in LVMI from baseline | At week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who had at least 1 class of improvement from baseline in New York Heart Association (NYHA) class at Week 48 |  | At week 48 | 
| Change from baseline in left atrial volume index (LAVI) at Week 48 |  | At week 48 | 
| Change from baseline in left ventricular mass index (LVMI) at Week 48 |  | At week 48 | 
| Incidence of major adverse cardiac events (MACE) |  | Up to 48 weeks | 
| Incidence of MACE-expanded events |  | Up to 48 weeks | 
| All-cause mortality |  | Up to 48 weeks | 
| Incidence of heart failure (HF) events |  | Up to 48 weeks | 
| Incidence of atrial fibrillation (AF)/atrial flutter |  | Up to 48 weeks | 
| Incidence of resuscitated cardiac arrest |  | Up to 48 weeks | 
| Incidence of ventricular tachyarrhythmias |  | Up to 48 weeks | 
| Incidence of nonvasovagal syncope and seizures |  | Up to 48 weeks | 
| Incidence of treatment emergent adverse events (TEAEs) |  | Up to 48 weeks | 
| Severity of TEAEs |  | Up to 48 weeks | 
| Incidence of treatment emergent serious adverse events (SAEs) |  | Up to 48 weeks | 
| Incidence of treatment emergent laboratory abnormalities |  | Up to 48 weeks | 
| Incidence of adverse events (AEs) |  | Up to 48 weeks | 
| Incidence of serious adverse events (SAEs) |  | Up to 48 weeks | 
| Incidence of AEs leading to discontinuation from study intervention |  | Up to 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Camyzos, BMS-986427, MYK-461, Mavacamten, Obstructive Hypertrophic Cardiomyopathy, Cardiac Magnetic Resonance Imaging (CMR)