Iscalimab, an anti-CD40 monoclonal antibody, significantly reduced proteinuria compared with placebo when added to standard-of-care therapy in patients with active proliferative lupus nephritis, a phase 2 trial finds. This phase 2, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT03610516) enrolled 57 patients with systemic lupus erythematosus and biopsy-proven lupus nephritis. Discontinuation rates were comparable between groups (46.2% iscalimab vs 44.4% placebo) with the primary cause physician decision during the COVID-19 pandemic. At week 24, patients in the iscalimab arm achieved a relative proteinuria reduction of 63.1% from baseline compared with 36.3% in the placebo arm. A greater effect of iscalimab emerged by week 12 and reached significance by week 24.