Efficacy and Safety Evaluation of Satralizumab in Patients with Type 1 Facioscapulohumeral Muscular Dystrophy: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** and **safety** of satralizumab compared with placebo in patients with Type 1 facioscapulohumeral muscular dystrophy (FSHD1). This objective is clinically relevant as it aims to determine the therapeutic potential and risk profile of satralizumab, a humanized anti-IL-6 receptor monoclonal antibody, in managing FSHD1, a progressive muscular disorder with limited treatment options.

Secondary objectives include assessing the long-term safety and efficacy of satralizumab during the open-label period. This will provide additional insights into the sustained effects and safety profile of the treatment over an extended duration, which is crucial for understanding its long-term viability as a therapeutic option for FSHD1.

The clinical trial involves a total of **12 participants** diagnosed with **Type 1 facioscapulohumeral muscular dystrophy** (FSHD1). The study population comprises both male and female subjects, aged between 18 and 65 years, who are in general good health, as indicated by their ability to walk without support and maintain a consistent level of exercise throughout the study. Participants were selected based on a genetically confirmed diagnosis of FSHD1, with specific criteria including a clinical severity score of 2 to 4 on the RICCI scale and a body weight of 100 kg or less. The trial does not include a vulnerable population. Participants are required to comply with study procedures, including maintaining their current exercise regimen and, for females of childbearing potential, adhering to contraceptive guidelines. The selection process ensures that participants have a stable lifestyle and are capable of understanding and consenting to the study requirements.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled study to evaluate the efficacy and safety of satralizumab in patients with **Type 1 facioscapulohumeral muscular dystrophy** (FSHD1). The trial will be conducted over a period of 96 weeks, with an estimated recruitment start date of January 1, 2024, and an estimated end date of January 1, 2028. Participants will be randomly assigned to receive either satralizumab or a placebo, both administered via subcutaneous injection. The primary objective is to assess the efficacy of satralizumab compared to placebo, with primary endpoints including changes in whole-body muscle MRI, RICCI clinical severity scale score, and muscle strength over a 48-week double-blind period. Secondary endpoints extend these assessments to a 96-week period, including an open-label phase.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, genetic confirmation of FSHD1, and clinical severity score. Participants will undergo baseline assessments, including MRI and laboratory tests. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and adherence to the treatment protocol. The end-of-study visit will conclude the participant's involvement, with final assessments to evaluate the long-term effects of the treatment.

Participant involvement is expected to last the full duration of the trial, approximately 96 weeks. However, conditions such as adverse events, non-compliance with study procedures, or withdrawal of consent may lead to early termination from the study. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent and are aware of their rights throughout the study.

The clinical trial involves the administration of **satralizumab**, marketed under the name Enspryng, which is a **solution for injection** in a pre-filled syringe. The active substance, satralizumab, is a humanized anti-IL-6 receptor monoclonal antibody. The pharmaceutical form is a solution for injection, and the route of administration is via **subcutaneous injection**. The dosage is 120 mg per injection, with a maximum daily dose of 120 mg and a total maximum dose of 3360 mg over the treatment period. The maximum treatment period is 96 weeks. The product is manufactured by Roche Registration GmbH and is authorized under the marketing authorization number EU/1/21/1559/001. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** that is identical in composition to satralizumab but does not contain the active ingredient. The placebo is used as a comparator treatment in this randomized, double-blind, placebo-controlled study. The placebo is administered in the same pharmaceutical form and via the same route as satralizumab, ensuring blinding of the treatment allocation. The placebo administration schedule mirrors that of the experimental medication to maintain consistency in the trial protocol.

The efficacy of satralizumab in the treatment of **Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1)** will be assessed through a series of primary and secondary endpoints over a specified period. The primary endpoints include evaluating changes from baseline to week 48 in whole body muscle MRI, RICCI clinical severity scale score, Reachable Work Space (RWS) results, muscle strength via quantitative isometric dynamometry, FSHD-Composite Outcome Measure (FSHD-COM) total score, FSHD-Rasch-built overall disability scale (FSHD-RODS) total score, and the proportion of participants showing improvement in the FSHD Patient Global Impression of Change (FSHD-PGIC) and FSHD Clinical Global Impressions of Change (FSHD-CGIC) scales. Additionally, changes in the number of falls reported, Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) total score, Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) total score, and inflammation biomarkers will be measured.

Secondary endpoints extend the evaluation period to week 96, including both the Double Blind (DB) and Open-label (OL) phases. The same parameters as the primary endpoints will be assessed, with the addition of safety and tolerability measures, such as the type, frequency, severity, and relationship of adverse events (AEs) to satralizumab, incidence of adverse events of special interest (AESIs), and the number of subjects discontinuing the study drug due to AEs. Clinically significant changes from baseline in laboratory tests, vital signs, and physical examination results will also be monitored. These assessments will be conducted using validated scales and instruments, ensuring a comprehensive evaluation of satralizumab's efficacy and safety in FSHD1 patients.