Phase 3 Open-Label Extension Study on Viltolarsen Safety and Efficacy in Ambulatory Male Patients with Duchenne Muscular Dystrophy

The primary objective of this Phase 3, multi-center, open-label extension study is to evaluate the **safety** and **tolerability** of viltolarsen administered intravenously at weekly doses of 80 mg/kg in boys with Duchenne Muscular Dystrophy (DMD) who have completed the NS-065/NCNP-01-301 study. Assessing safety and tolerability is crucial for determining the potential risks associated with long-term use of viltolarsen in this patient population, thereby informing clinical decision-making and patient management strategies.

Secondary objectives include: - Comparing the efficacy of viltolarsen administered intravenously at weekly doses of 80 mg/kg over a 96-week treatment period versus natural history controls. This comparison will utilize strength and endurance outcomes to determine the therapeutic benefit of viltolarsen in maintaining or improving physical function in boys with DMD.

The clinical trial involves a total of **53 participants** diagnosed with **Duchenne Muscular Dystrophy (DMD)**. The study population consists exclusively of male subjects, specifically boys who have previously completed the NS-065/NCNP-01-301 study. Participants are categorized within a specific age range, although the exact ages are not detailed in the provided data. The selection process for the trial population required that participants have completed the prior study, and that their parent(s) or legal guardian(s) provided written informed consent. Additionally, participants and their guardians must be willing and able to comply with the study's scheduled visits and procedures. The trial does not include female subjects and is focused on a vulnerable population, given the nature of the medical condition being studied. No specific lifestyle considerations such as diet or physical activity are mentioned in the available data.

The clinical trial is a **Phase 3, multi-center, open-label extension study** designed to assess the safety and efficacy of **Viltolarsen** in ambulant boys with **Duchenne Muscular Dystrophy (DMD)**. The primary objective is to evaluate the safety and tolerability of Viltolarsen administered intravenously at weekly doses of 80 mg/kg in participants who have completed the NS-065/NCNP-01-301 study. The trial is expected to run from April 13, 2021, to August 20, 2025, with a maximum treatment period of 96 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the completion of the prior study and the provision of informed consent by the patient's parent(s) or legal guardian(s). The study will include regular follow-up visits to monitor vital signs, conduct physical examinations, and perform clinical laboratory tests, including hematology, clinical chemistry, urinalysis, and urine cytology. Additional assessments will include antibodies to dystrophin and Viltolarsen, 12-lead electrocardiograms (ECGs), renal ultrasounds, and monitoring for treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Secondary endpoints will evaluate functional outcomes such as the Time to Stand Test (TTSTAND), Time to Run/Walk 10 Meters Test (TTRW), Six-minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), Time to Climb 4 Stairs Test (TTCLIMB), and quantitative muscle strength measured by hand-held dynamometer. The expected length of participant involvement is up to 96 weeks, with conditions for early termination including the inability to comply with scheduled visits, investigational product administration, or study procedures. The trial is not classified as low intervention and is categorized as a Category 2 trial, adhering to EMA guidance on disclosure rules.

The clinical trial involves the administration of **Viltolarsen**, an experimental medication designed for the treatment of **Duchenne Muscular Dystrophy (DMD)**. Viltolarsen is provided in the form of a **solution for infusion**. The active substance, viltolarsen, is a nucleic acid-based **antisense oligonucleotide**. The pharmaceutical form is specifically tailored for pediatric use, and the medication is administered intravenously. The dosing regimen consists of a weekly infusion at a dose of 80 mg/kg. The maximum total dose permissible over the course of the treatment is 7680 mg/kg, with a maximum treatment period of 96 weeks.

In this study, Viltolarsen is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is an open-label extension study, which implies that all participants receive the experimental treatment without a blinded control group. Participant compliance with the dosing schedule is monitored through regular assessments to ensure adherence to the treatment protocol.

The efficacy of Viltolarsen in the treatment of **Duchenne Muscular Dystrophy (DMD)** will be assessed through a series of primary and secondary endpoints. Primary endpoints include vital signs, physical examination, clinical laboratory tests such as hematology, clinical chemistry, urinalysis, and urine cytology, as well as antibodies to dystrophin and viltolarsen. Additionally, a 12-lead electrocardiogram (ECG), renal ultrasound, and monitoring of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be conducted.

Secondary endpoints focus on functional assessments and include the Time to Stand Test (TTSTAND), Time to Run/Walk 10 Meters Test (TTRW), Six-minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and Time to Climb 4 Stairs Test (TTCLIMB). Quantitative muscle strength will be measured using a hand-held dynamometer, specifically evaluating elbow extension, elbow flexion, knee extension, and knee flexion on the dominant side only. These assessments will provide comprehensive data on the efficacy of Viltolarsen in improving muscle function and overall physical performance in patients with DMD.