Long-term Safety and Efficacy Evaluation of Vamorolone in Duchenne Muscular Dystrophy Patients Post-Completion of Prior Vamorolone Studies

The primary objective of this study is to evaluate the **safety** of long-term treatment with vamorolone in boys with **Duchenne Muscular Dystrophy** (DMD) concerning vertebral fractures. This is clinically relevant as vertebral fractures can significantly impact the quality of life and mobility in patients with DMD, a progressive neuromuscular disorder.

Secondary objectives include:

• Evaluating the safety of long-term treatment with vamorolone in boys with DMD on non-vertebral fractures, cataracts, and delayed puberty.
• Assessing the overall safety of long-term treatment with vamorolone in boys with DMD.
• Evaluating the long-term treatment effect of vamorolone on ambulatory and non-ambulatory function.

The clinical trial involves a total of **39 participants** diagnosed with **Duchenne Muscular Dystrophy**. The study population consists exclusively of male subjects, specifically boys, as indicated by the age range category code "2," which typically corresponds to a pediatric population. Participants were selected based on their previous completion of either the VBP15-LTE or VBP15-004 study and their transition through the CUP, NPP, or EAP, ensuring they are already on vamorolone at the time of enrollment. The trial focuses on evaluating the safety of long-term treatment with vamorolone concerning vertebral fractures. The study population is considered vulnerable, given the nature of the disease and the age of the participants. The trial does not include female subjects, and no specific lifestyle considerations such as diet or physical activity are mentioned. The sponsor has not provided additional information regarding the general health status or lifestyle habits of the participants.

The clinical trial is designed as an **open-label**, multi-center study to evaluate the long-term safety and effectiveness of **vamorolone** in boys with **Duchenne Muscular Dystrophy** (DMD) who have completed prior studies with the drug. The primary objective is to assess the safety concerning vertebral fractures, with secondary endpoints including the incidence of non-vertebral fractures, cataracts, and other health metrics such as body weight, height, and body mass index (BMI). The trial will also monitor the frequency of adverse events and serious adverse events, as well as changes in physical performance tests like the 6-Minute Walk Test (6MWT) and the Time to Stand Test (TTSTAND).

Participants will be involved in the study for a maximum treatment period of 48 months. The trial is expected to start recruitment on October 31, 2024, and conclude by October 31, 2028. The study will include an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will finalize data collection and assess the long-term impact of the treatment. Participants must have completed previous studies with vamorolone and be on the medication at the time of enrollment. Written informed consent from the participant or their legal guardian is required, and they must be willing to comply with the study protocol.

Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or any adverse events that pose a significant risk to the participant's health. The study aims to provide comprehensive data on the long-term use of vamorolone in managing DMD, contributing valuable insights into its safety profile and therapeutic benefits.

The clinical trial involves the administration of **AGAMREE 40 mg/ml oral suspension**, which contains the active substance **vamorolone**. This experimental medication is formulated as an oral suspension and is intended for oral use. The maximum daily dose of vamorolone is 240 mg, with a total dose not exceeding 6 mg/kg. The treatment period is capped at 48 weeks. Vamorolone is classified under the ATC code H02AB, indicating its categorization as a glucocorticoid. The chemical origin of the active substance is confirmed, and the product is not specifically formulated for pediatric use. The trial aims to evaluate the safety and effectiveness of long-term treatment with vamorolone in boys with Duchenne Muscular Dystrophy (DMD).

In addition to the experimental treatment, the study may involve the use of other glucocorticoids as non-experimental treatments. These glucocorticoids serve as a comparator to assess the relative safety and efficacy of vamorolone. The administration of these treatments will follow standard protocols, ensuring that participants receive consistent and reliable care throughout the trial. Compliance with dosing schedules will be monitored to maintain the integrity of the study data and ensure participant safety.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the number of vertebral fractures per 1000 person-years, determined via X-ray central reading. Secondary endpoints include the time to first vertebral fractures (cumulative incidence), the number of non-vertebral fractures per 1000 person-years based on investigator reporting, and the time to first non-vertebral fractures (cumulative incidence). Additional secondary endpoints involve the number of cataracts per 1000 person-years assessed by an ophthalmologist, the number of subjects not reaching Tanner stage 2 by 15 years of age, and the frequency of adverse events (AEs) and serious adverse events (SAEs).

Further secondary endpoints include changes from baseline in body weight, height, and body mass index (BMI), the number of subjects with clinically relevant laboratory abnormalities such as glycosylated hemoglobin (HbA1c) and morning cortisol levels, and changes from baseline in the Time to Stand Test (TTSTAND) velocity. The 6-Minute Walk Test (6MWT) distance and changes from baseline in 6MWT distance will also be evaluated, along with NorthStar Ambulatory Assessment (NSAA) scores and the age at ambulatory and non-ambulatory milestones. These efficacy parameters will be collected and analyzed throughout the trial to assess the long-term effectiveness of **vamorolone** in boys with Duchenne Muscular Dystrophy.