Impact of satralizumab on bone strength and muscle function in Duchenne muscular dystrophy (DMD): design of the SHIELD-DMD study

Topic:

Clinical Trials

Poster Number: P82

Author(s):

Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Christian De Ford, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Maitea Guridi, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Carlos Estevez-Fraga, Roche Products Ltd, Welwyn, United Kingdom, Robbie Peck, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Siân Lennon-Chrimes, Roche Products Ltd, Welwyn, United Kingdom, Kathleen Blondeau, Parexel Belgium SRL, Wavre, Belgium, Christopher Craggs, Genentech, Inc., South San Francisco, CA, USA, Venissa Machado, Roche Innovation Center Basel, Basel, Switzerland, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Anna Kostera-Pruszczyk, Medical University of Warsaw, Warsaw, Poland, Andres Nascimento, MD, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER – ISC III, Barcelona, Spain, Leanne Ward, MD, FRCPC, Children’s Hospital of Eastern Ontario, Eugenio Mercuri, MD, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy

Background: DMD is characterized by progressive muscle atrophy, chronic inflammation and low bone mass causing bone fragility, which is exacerbated by long-term corticosteroids. In DMD, elevated interleukin (IL)-6 is associated with muscle atrophy, increased inflammatory response and increased bone resorption; IL-6 receptor (IL-6R) concentration is also negatively correlated with total body less head bone mineral density (BMD) Z-score. In rheumatoid arthritis, anti-IL-6R monoclonal antibody (mAb) therapy inhibits IL-6 signaling, leading to reduced inflammation and fibrosis, and balances bone remodeling in favor of formation. SHIELD-DMD (NCT06450639) is an open-label Phase 2 study evaluating the impact of satralizumab, a humanized, recycling anti-IL-6R mAb, on bone strength and muscle function in DMD.

Methods: SHIELD-DMD is enrolling boys with DMD who are receiving daily corticosteroids. Group 1 includes ambulatory and non-ambulatory boys aged ≥8 to <16 years with existing low-trauma fractures (n=16). Group 2 includes fracture-naïve ambulatory boys aged ≥8 to <12 years (n=34). Initially, non-ambulatory boys aged ≥12 years (n=8) will be enrolled into Group 1, with subsequent enrolment gated on interim safety and pharmacokinetics (PK). Fixed doses of subcutaneous satralizumab (determined by baseline weight) are administered at baseline, Week 2 and Week 4 and every 4 weeks thereafter for a total duration of 2 years. Endpoints include change from baseline to Week 52 in lumbar spine (LS) BMD Z-score with appropriate bone size adjustments in fracture-naïve patients (primary), change from baseline in LS BMD Z-score and serum bone turnover markers in all patients, the proportion of patients with new low-trauma long bone or vertebral fractures and the mean number of fractures per patient, and change from baseline in rise from the floor velocity. Safety, PK and immunogenicity will be assessed. Conclusions: SHIELD-DMD is the first trial in DMD to evaluate IL-6R inhibition as a mechanism for improving bone strength and muscle function.