Long-Term Safety and Efficacy Evaluation of Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy Patients from Previous Clinical Studies

The primary objective of this Phase 3, multinational, long-term follow-up study is to evaluate the long-term **safety** of **delandistrogene moxeparvovec** in subjects with **Duchenne Muscular Dystrophy** who have previously received SRP-9001 in a clinical study. Assessing the safety profile over an extended period is clinically relevant as it provides critical information on the potential risks associated with the treatment, ensuring that the benefits outweigh any adverse effects for patients undergoing this gene therapy.

Secondary objectives include:

• To evaluate the long-term **efficacy** of delandistrogene moxeparvovec. This assessment is crucial for determining the sustained therapeutic benefits of the treatment, which can inform clinical decision-making and patient management strategies.

The clinical trial involves a total of **319 participants** diagnosed with **Duchenne Muscular Dystrophy**. The study population is exclusively male, with an age range that includes both children and adolescents. Participants were selected based on their prior receipt of delandistrogene moxeparvovec in a previous clinical study. The trial focuses on a vulnerable population, ensuring that participants have the capacity, either personally or through a legal caregiver, to comply with the study's requirements. The trial does not include female subjects, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is a **Phase 3**, multinational, long-term follow-up study designed to evaluate the safety and efficacy of **delandistrogene moxeparvovec** in subjects who have previously received the treatment in a prior clinical study. The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. The estimated duration of the trial extends until November 15, 2030, with recruitment anticipated to commence on May 29, 2024. Participants will be involved in the study for a period of up to five years, during which they will undergo a series of structured study visits.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as prior receipt of delandistrogene moxeparvovec for **Duchenne Muscular Dystrophy** and the ability to comply with the study protocol. Follow-up visits are scheduled at regular intervals to monitor the primary endpoint, which is the number of participants experiencing treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Secondary endpoints include changes in various functional and physiological assessments from pre-infusion baseline to five years post-infusion, such as the North Star Ambulatory Assessment (NSAA) total score, time to rise from the floor, and cardiac and musculoskeletal MRI findings.

The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted to gather comprehensive data on the long-term effects of the treatment. Participants may be subject to early termination from the study if they experience significant adverse events or if they are unable to adhere to the study protocol. The trial is not classified as low intervention, reflecting the complexity and rigor of the study design. The investigational product, delandistrogene moxeparvovec, is administered via **intravenous use** in the form of a solution for injection/infusion, with a maximum total dose amount specified. The study is conducted under the sponsorship of Sarepta Therapeutics Inc., with the product designated as an orphan drug, highlighting its relevance in treating a rare disease.

The clinical trial involves the administration of **Delandistrogene moxeparvovec-rokl**, an experimental gene therapy product. This investigational medicinal product is formulated as a **solution for injection/infusion** and is intended for **intravenous use**. The active substance, **delandistrogene moxeparvovec**, is a structurally diverse substance designed to deliver a gene of interest, specifically the dystrophin gene, using an adeno-associated virus (AAV) vector. The maximum total dose administered is 13,300,000,000,000 vector genomes (vg) per milliliter, with a treatment period limited to a single administration. This product is designated as an orphan drug and is specifically formulated for pediatric use.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the long-term safety and efficacy of the experimental product, **Delandistrogene moxeparvovec-rokl**. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol. The trial aims to provide comprehensive data on the safety profile of the gene therapy in subjects who have previously received SRP-9001 in a clinical study.

The efficacy of **delandistrogene moxeparvovec** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the safety profile, specifically the number of participants experiencing a Treatment-emergent Adverse Event (TEAE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI). Secondary endpoints are designed to evaluate functional and physiological changes over a long-term period, specifically from pre-infusion baseline to five years post-infusion.

Secondary efficacy assessments will include changes in the North Star Ambulatory Assessment (NSAA) Total Score, Time to Rise from Floor, and Time of 10-meter Walk/Run (10MWR). Additionally, changes in the Performance of Upper Limb (PUL) Version 2.0 Total Scores and Domain Specific Scores will be measured. Pulmonary function will be evaluated through changes in Forced Vital Capacity Percent (FVC%) Predicted and Peak Expiratory Flow Percent (PEF%) Predicted. Cardiac and musculoskeletal health will be monitored via changes in Magnetic Resonance Imaging (MRI) findings.

These efficacy parameters will be collected and analyzed at specified intervals, with the primary focus on the long-term follow-up of participants who have previously received the treatment. The assessments will utilize validated scales and imaging techniques to ensure accurate and reliable data collection. The trial is structured to provide comprehensive insights into the long-term efficacy and safety of delandistrogene moxeparvovec in individuals with Duchenne muscular dystrophy.