Long-term Safety and Biomarker Assessment of EDG-5506 in Adults and Adolescents with Becker Muscular Dystrophy: An Open-Label Extension Study

The primary objective of this study is to assess the **safety** and tolerability of long-term treatment with sevasemten in individuals diagnosed with Becker Muscular Dystrophy. This is clinically relevant as it aims to determine the potential risks and adverse effects associated with prolonged use of the investigational drug, which is crucial for ensuring patient safety and guiding future therapeutic strategies.

Secondary objectives include:

• To assess the change in individual safety parameters. This evaluation is important for understanding the specific safety profile of the treatment and identifying any changes in health indicators that may occur over the course of the study.

The clinical trial involves a total of **236 participants** diagnosed with **Becker Muscular Dystrophy**. The study population is exclusively male, with an age range that includes both adolescents and adults, contingent upon regulatory approval in respective countries. Participants were selected based on their prior involvement in specific studies (EDG-5506-002, EDG-5506-201, or EDG-5506-202) and their completion of designated study visits. The trial does not include a vulnerable population, and female subjects are not part of this study. Participants are expected to adhere to specific lifestyle considerations, such as compliance with contraception requirements as outlined in the study protocol. The general health status of participants is not specified beyond their diagnosis of Becker Muscular Dystrophy.

The clinical trial is designed to evaluate the long-term safety and efficacy of **EDG-5506** in individuals diagnosed with Becker Muscular Dystrophy. This study is a Phase IV, open-label extension trial, which aims to assess the safety, biomarkers, and functional measures in both adults and adolescents. The trial is structured as a non-randomized, open-label study, allowing for the continuous monitoring of participants who have previously completed specific prior studies involving EDG-5506. The trial is expected to commence on December 26, 2023, and conclude by August 3, 2029, with a maximum treatment period of 18 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as prior participation in related studies and the ability to comply with study requirements. Following the screening, participants will enter the treatment phase, where they will receive EDG-5506 orally in tablet form, with a maximum daily dose of 10 mg. Regular follow-up visits will be scheduled to monitor the incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs), as well as to assess treatment-emergent laboratory abnormalities, changes in safety labs, vital signs, ECG parameters, cardiac function, and pulmonary function.

The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments will be conducted to evaluate the long-term effects of the treatment. The expected length of participant involvement is up to 18 months, contingent upon adherence to the study protocol. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events that warrant discontinuation of treatment. The study is conducted in accordance with regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **EDG-5506**, an investigational medication developed by Edgewise Therapeutics Inc. **EDG-5506** is formulated as a **tablet** and is intended for oral administration. The active substance, also named **EDG-5506**, is of chemical origin. The maximum daily dose is 10 mg, with a total maximum dose of 10,960 mg over the course of the study. The treatment period extends up to 18 months. The trial aims to assess the long-term effects of **EDG-5506** on safety, biomarkers, and functional measures in adults and adolescents with Becker Muscular Dystrophy.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of **EDG-5506**. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not include any pediatric formulations, and the investigational product is not classified as an orphan drug. The study is designed to evaluate the safety and tolerability of long-term treatment with **EDG-5506**.

The efficacy of the clinical trial assessing the long-term effect of **EDG-5506** in adults and adolescents with Becker Muscular Dystrophy will be evaluated using specific endpoints. The primary endpoint focuses on the incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs) in participants treated with sevasemten. Secondary endpoints include the incidence of treatment-emergent abnormal laboratory test results, encompassing clinical chemistry and hematology. Additionally, changes from baseline will be measured in safety laboratory parameters, vital signs, electrocardiogram (ECG) parameters, cardiac function as assessed by echocardiogram, and pulmonary function as assessed by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).