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)

The primary objective of this study is to evaluate the efficacy of **mavacamten** in reducing the thickness of the heart wall (ventricle) and the size of the upper heart chamber (atria) in patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy, as assessed by cardiac magnetic resonance imaging (CMR). This is clinically relevant as it may provide insights into the potential of mavacamten to alleviate structural cardiac abnormalities associated with this condition, potentially improving patient outcomes.

Secondary objectives include: - Exploring the effect of mavacamten on the New York Heart Association (NYHA) functional classification, which is crucial for assessing the impact on patients' functional status and quality of life. - Monitoring safety events during the study period to ensure the treatment's safety profile is well-characterized.

The clinical trial involves a total of **70 participants** diagnosed with **Symptomatic Obstructive Hypertrophic Cardiomyopathy**. The study population includes both male and female adults, specifically those classified under the New York Heart Association (NYHA) Functional Class II or III, indicating a moderate level of heart failure symptoms. Participants are selected based on their eligibility as adults with symptomatic obstructive hypertrophic cardiomyopathy. The age range of the participants spans from 18 to 64 years, encompassing both younger and middle-aged adults. The trial does not specify particular lifestyle considerations such as diet or physical activity. The selection process includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across different demographic groups. The trial aims to evaluate the impact of mavacamten on reducing heart wall thickness and the size of the upper heart chamber through cardiac magnetic resonance imaging.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy of **mavacamten** in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The primary objective is to assess the impact of mavacamten on reducing heart wall thickness and the size of the upper heart chamber, as measured by cardiac magnetic resonance imaging (CMR) at week 48. The trial will also evaluate the improvement in heart failure class and monitor for other cardiac events as a safety assessment. The study is expected to commence on November 20, 2023, and conclude by November 20, 2026, with a total duration of approximately three years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as symptomatic oHCM with New York Heart Association (NYHA) Functional Class II or III. Following randomization, participants will receive either mavacamten or a placebo in capsule form, administered orally. The trial includes multiple follow-up visits to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will involve a comprehensive evaluation of the primary and secondary endpoints, including CMR imaging to assess changes in myocardial structure.

The expected length of participant involvement is up to 96 weeks, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity of the double-blind design throughout the study period. Participants will be closely monitored to ensure compliance with the study protocol and to address any safety concerns promptly.

The clinical trial involves the administration of **Mavacamten**, a chemical compound with the active substance name **Mavacamten**. It is provided in capsule form, with available dosages of 2.5 mg, 5 mg, 10 mg, and 15 mg per capsule. The pharmaceutical form is a solid oral dosage, and the route of administration is oral. The maximum daily dose is 15 mg, and the treatment period extends up to 96 weeks. The capsules are manufactured by Bristol-Myers Squibb International Corporation and are identified by the sponsor product code BMS-986427/MYK-461. The chemical structure of Mavacamten is also known by several synonyms, including MYK-461 and SAR439152.

The study also includes a placebo group, which receives a placebo designed to match the Mavacamten capsules in appearance. The placebo is a solid oral dosage form contained in size 2 gelatin capsules, each filled with 120 mg of an excipient blend. This placebo is intended to mimic the active Mavacamten capsules across all active strengths, ensuring blinding in the double-blind study design. The placebo does not contain any active pharmaceutical ingredient and serves as a control to evaluate the efficacy and safety of Mavacamten in the treatment of symptomatic obstructive hypertrophic cardiomyopathy.

The efficacy of **mavacamten** in the clinical trial will be assessed primarily by evaluating the reduction in heart wall thickness and the size of the upper heart chamber (atria) at week 48 using cardiac magnetic resonance (CMR). This primary endpoint aims to determine the impact of mavacamten on myocardial structure in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Secondary endpoints include assessing the improvement in heart failure class according to the New York Heart Association (NYHA) Functional Class and monitoring for other cardiac events as part of a safety assessment.