402 Study design and rationale for the efficacy and safety assessment of daxdilimab, a selective plasmacytoid dendritic cell depleter, in a phase 2 trial of patients with moderate-to-severe primary discoid lupus erythematosus

Background

Daxidilimab (DAX) is an IgG1λ afucosylated monoclonal antibody specific for immunoglobulin-like transcript 7 (ILT7), a cell-surface protein that is exclusively expressed on plasmacytoid dendritic cells (pDCs). DAX binds to ILT7 on the surface of pDCs, resulting in their depletion via antibody-dependent cellular cytotoxicity. Several autoimmune disorders, including discoid lupus erythematosus (DLE), show marked enrichment of pDCs and interferon activity in affected tissue. DLE is considered the most challenging scarifying skin manifestation to treat for which a successful therapy does not currently exist.

Methods

This is a 60-week Phase 2, multicenter, randomized, double-blind, placebo- controlled, parallel-group trial to investigate the efficacy and safety of DAX in reducing disease activity in adult participants with moderate-to-severe primary DLE refractory to standard of care therapy (NCT05591222, figure 1). Approximately 99 participants will be randomized in a ratio of 1:1:1 (33 participants per group) to receive subcutaneous injection of DAX arm 1, DAX arm 2, or placebo. Administration of trial intervention will occur every four weeks starting from Day 1 through Week 44. After week 24 all participants will be receiving DAX, including those assigned to the placebo arm, for the remainder of the 48-week treatment period.

Outcome Measures

The primary efficacy endpoint is the mean change in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score from baseline to Week 24. Secondary efficacy endpoints include the proportion of participants who achieve 0 or 1 on the Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) scale at Week 24 (5-point Likert scale [0–4]), proportion of participants who achieve a ≥ 50% reduction in CLASI-A score from baseline at Week 24, and mean change in the Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE) from baseline to Week 24. Safety and tolerability of DAX will be assessed via the incidence of adverse events (AEs), serious AEs, and AEs of special interest. Pharmacokinetics and effects on pharmacodynamics and other biomarkers of interest will also be assessed.

Conclusion

There is a significant unmet need for novel, fast-acting, and safe new therapies to reduce disease activity and damage and improve the quality of life for patients living with DLE. This is a proof-of-concept study that aims to evaluate a potentially new therapy in subjects with DLE.