DARALUPA Monocenter, Open Label Study to Evaluate the Safety and Efficacy of Daratumumab in Combination With Standard Background Therapy in Participants With Moderate to Severe Systemic Lupus Erythematosus

This clinical trial "DARALUP" is designed to evaluate the efficacy and safety of daratumumab, a monoclonal antibody directed against CD38, in patients with systemic lupus erythematosus (SLE). This is a monocenter, open-label Phase II trial recruting SLE patients with clinical and serologic activity despite state-of-the-art immunosuppressive therapy. Treatment in this study will be Weekly daratumumab injections over a period of 8 weeks. This study will enroll 10 patients. SLE is a sometimes severe, generalized autoimmune disease with few approved therapies to date. Therefore, the planned study offers an opportunity to identify a new, targeted therapeutic approach. Daratumumab has been studied in multiple Phase III clinical trials in patients with relapsing multiple myeloma, a plasma cell malignancy, where it demonstrated efficacy with an acceptable safety profile and has been approved since 2016 under the trade name Darzalex®. The aim is to investigate whether daratumumab provides clinically significant efficacy in SLE, another disease in which plasma cells have been shown to play a pathogenic role. Previous experience by the sponsor of this trial with the use of daratumumab in two patients with SLE suggests that one cycle of 4 weekly infusions with 16 mg/kg daratumumab was associated with a significant serologic and clinical response. In this study, a dosing regimen of 2 cycles of Darzalex is planned, with one cycle containing 4 Weekly injections. Based on the previously reported efficacy under anti-CD38 therapy, this human monoclonal antibody appears suitable for the therapy of SLE and will be investigated in this study.