Background and aims Binding of CD40 ligand (CD40L) to CD40 activates B cells, antigen-presenting cells and platelets. Evidence suggests CD40L blockade might provide an effective treatment for systemic autoimmune disorders, including systemic lupus erythematosus (SLE). We report data from a Phase I double-blind, multiple dose study (NCT01764594) of dapirolizumab pegol (DZP), a PEGylated anti-CD40L Fab’ fragment, in SLE patients.

Methods Twenty-four SLE patients were randomised (2:1, stratified by the presence of anti-phospholipid antibodies) to receive DZP (loading dose 30 mg/kg, then 15 mg/kg every 2 weeks for 10 weeks) or placebo. Patients were followed for 18 weeks. Objectives: safety and tolerability of DZP (primary); disease activity measures (BICLA and SRI-4; exploratory). Genes expressed by plasma cells, B cells, other immune cells and transcripts associated with SLE disease activity were analysed by qPCR.

Results No serious adverse events (AEs), thromboembolic events or deaths occurred. Most treatment-emergent AEs (TEAEs) were mild or moderate, transient, and resolved without intervention. Nasopharyngitis was the most common TEAE (6 patients in the DZP group; none with placebo). One patient withdrew due to upper respiratory tract infection (DZP group). Of DZP-treated patients evaluable for BICLA and SRI-4, 46% and 42% respectively, responded by Week 12 (vs 14% placebo; Table 1). Rapid and maintained mechanism-related gene expression changes were observed, particularly in plasma cell genes (IgA, IgG, IgJ) from the DZP group.

• Download figure
• Open in new tab
• Download powerpoint

Table 1

Conclusions DZP was well tolerated and demonstrated improvement in clinical measures of disease activity. A Phase II study is evaluating efficacy and safety of DZP in SLE patients (NCT02804763).