Abstract
Objective
Describe the study design and results of a phase 2/3 study of ulviprubart for treatment of inclusion body myositis (IBM).
Background
IBM is a rare, progressive disorder characterized by invasion of muscle by highly differentiated cytotoxic CD8+ T cells. IBM can cause difficulty walking, loss of grip strength, and dysphagia. There are no pharmacological treatments approved for IBM. Ulviprubart, a humanized monoclonal antibody, selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting KLRG1 expressed on most IBM-muscle–infiltrating T cells.
Design/Methods
This randomized, double-blind, placebo-controlled trial (NCT05721573) included patients aged ≥40 years with an IBM diagnosis otherwise fulfilling 2011 European Neuromuscular Center criteria. Ulviprubart (0.5 or 2.0 mg/kg) or placebo (1:1:1) was administered subcutaneously every 8 weeks for 76 weeks, with the option to receive treatment at 2.0 mg/kg in an open-label extension study. Efficacy endpoints included mean changes from baseline to week 76 in Inclusion Body Myositis Functional Rating Scale (IBMFRS; primary), manual muscle testing (MMT) of 23 muscle groups converted to a Kendall score, hand grip and quadriceps strength by dynamometry, and modified Timed Up and Go (mTUG). Safety monitoring included assessment of treatment-emergent adverse events.
Results
Overall, 272 patients were enrolled. Mean (SD) patient age at baseline was 68.1 (7.8) years, and 186 patients were male (68%). Mean (SD) age at diagnosis was 65.1 (8.1) years. Mean (SD) baseline IBMFRS score was 27.3 (5.0); 14 patients had baseline IBMFRS scores of <20, 63 had scores of 20–24, and 195 had scores of ≥25. Mean (SD) baseline values for MMT, grip strength (dominant), quadriceps strength (dominant), and mTUG score were 7.8 (1.2), 11.7 (7.0) kg, 11.0 (7.6) kg, and 0.32 meters/second, respectively.
Conclusions
This is the largest prospective interventional study of patients with IBM with a range of clinically significant disease burden. Topline efficacy and safety results will be presented.