637P ReInForce: a bicentric, randomized, double blind, placebo-controlled pilot study to evaluate the efficacy and safety of satralizumab in FSHD1.

Facioscapulohumeral muscular dystrophy (FSHD) is marked by progressive muscle weakness in facial, shoulder girdle, upper arms, lower limbs, and abdominal muscles, causing considerable morbidity and decreasing quality of life. There are currently no approved therapies for FSHD. The primary form, FSHD1, is linked to harmful overactivity of the DUX4 gene, resulting in muscle atrophy and weakness. Studies indicate that abnormal DUX4 expression triggers inflammatory processes in the initial stages of the disease. Patients with FSHD1 had increased inflammatory and reduced anti-inflammatory cytokines levels, indicating chronic inflammation. IL-6 levels strongly correlate with clinical severity in patients, and with functional scores in patients and FSHD-like mouse models. Here we present the study design of ReInForce (NCT06222827), a bicentric, randomized, double-blind, placebo-controlled, Phase 2 study to investigate the safety and efficacy of satralizumab, an IL-6 receptor inhibitor, in adults with FSHD1. Patients (N=40) will receive 120 mg satralizumab or placebo subcutaneously at Weeks 0, 2, 4 and then every 4 weeks until Week 48. The 48 weeks of the Double-Blind period will be followed by a 48-week Open Label period. The study will evaluate efficacy by assessing changes in muscle composition and function, as well as measures of clinical disease progression. Given the pathological relevance of inflammation in FSHD, and the correlation of IL-6 levels with disease severity, satralizumab may reduce muscle and systemic inflammation, thereby reducing fibrofatty degeneration in FSHD. [ABSTRACT FROM AUTHOR]