Evaluation of Deflazacort Efficacy in LMNA-Related Congenital Muscular Dystrophy: A Study on Clinical Outcomes and Biomarker Identification

The primary objective of this study is to evaluate the effect of **Deflazacort** therapy, administered as oral drops at a dosage of 0.9 mg/kg/day, on the clinical outcome and secretome in both adult and pediatric patients diagnosed with LMNA-related congenital muscular dystrophy (L-CMD). This investigation is clinically relevant as it aims to determine the therapeutic efficacy of Deflazacort, a glucocorticoid, in improving patient outcomes in a condition characterized by progressive muscle weakness and degeneration. The study seeks to provide insights into the potential benefits of Deflazacort in managing L-CMD, thereby contributing to the optimization of treatment strategies for this rare form of muscular dystrophy.

The clinical trial focuses on evaluating the effect of Deflazacort therapy in patients diagnosed with **Laminopathies**, specifically L-CMD and EDMD2. The study population includes both male and female participants, aged between 3 to 40 years, who are of Caucasian origin. Participants are required to be corticosteroid-naïve and must have a clinical and genetic diagnosis of L-CMD or EDMD2 with an age onset before 5 years. The trial does not involve a vulnerable population. Participants must be able to provide reproducible measurements of forced vital capacity (FVC) with less than 15% variability between two repeated measures at the time of recruitment. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effect of **deflazacort** oral drops, administered at a dosage of 0.9 mg/kg/day, on clinical outcomes and secretome in patients with laminopathies, specifically LMNA-related congenital muscular dystrophy (L-CMD). This is a Phase 4, randomized, double-blind, controlled trial, with an estimated duration from March 31, 2021, to March 6, 2025. The trial aims to assess the primary endpoint, which involves evaluating the effects of treatment on clinical parameters at various treatment times and follow-up intervals, specifically at T0, T6, T12, T15, and T18 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical and genetic diagnosis, and the ability to provide reproducible measurements of forced vital capacity (FVC). Following the screening, participants will be randomized and begin treatment with deflazacort. Follow-up visits will occur at specified intervals to monitor clinical outcomes and ensure adherence to the treatment protocol. The end-of-study visit will conclude the trial, where 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, with conditions for early termination including adverse reactions to the treatment, non-compliance with the study protocol, or withdrawal of consent. Participants are required to provide informed consent, and in the case of minors, consent must be obtained from a parent or legal guardian. The trial is conducted under the authorization of relevant regulatory bodies, ensuring adherence to ethical standards and scientific rigor.

The clinical trial involves the administration of **Deflazacort**, marketed under the name DEFLAN 22,75 mg/ml oral drops, suspension. This experimental medication is formulated as an oral suspension and is administered via **buccal use**. The dosage is set at 0.9 mg/kg/day, with a maximum total dose amounting to 3942 mg/kg over the course of the treatment. The maximum treatment period is 12 months. The active substance, **Deflazacort**, is a glucocorticoid of chemical origin, and the product is manufactured by Laboratori Guidotti S.P.A. The medication is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the clinical effectiveness of Deflazacort in patients with LMNA-related congenital muscular dystrophy. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the impact of Deflazacort on clinical outcomes and secretome in both adult and pediatric populations.

Efficacy in this clinical trial will be assessed by evaluating the effects of treatment with Deflazacort drops at a dosage of 0.9 mg/kg/day. The primary endpoint involves the assessment of changes in clinical parameters at specified treatment and follow-up timepoints, which include T0, T6, T12, T15, and T18. These timepoints are strategically chosen to monitor the progression and response to the treatment over the course of the trial. The trial aims to evaluate the clinical outcome and secretome in both adult and pediatric patients diagnosed with LMNA-related congenital muscular dystrophy (L-CMD). The efficacy assessment will focus on the improvement of clinical parameters, which are expected to reflect the therapeutic impact of Deflazacort. The trial is designed to provide a comprehensive evaluation of the treatment's effectiveness, contributing to the understanding of its clinical benefits in the target patient population.