Patients with circulating anti-glomerular basement membrane (GBM) antibodies and significant renal damage have a dismal prognosis for kidney survival. It was unclear whether using an endopeptidase that cleaves circulating and kidney-bound IgG can improve the prognosis. A phase 2a one-arm investigator-driven trial (EudraCT 2016–004082–39) was conducted in 17 hospitals across five European nations. About 15 people with circulating anti-GBM antibodies and an eGFR of 15 ml/min per 1.73m^2 were given a single dose of 0.25 mg/kg imlifidase. All patients underwent normal cyclophosphamide and corticosteroid therapy, although plasma exchange was only performed if autoantibodies rebounded. At 6 months, the key objectives were safety and dialysis independence.
About 10 patients were dialysis-dependent at the time of inclusion, while the remaining five had eGFR values ranging from 7 to 14 ml/min per 1.73m^2. The median age was 61 years (range 19–77), 6 were female, and 6 had anti-neutrophil cytoplasmic antibodies. Then, 6 hours after receiving imlifidase, all patients exhibited anti-GBM antibody levels that were below the reference range of a prespecified test. At 6 months, 67% (10 out of 15) were dialysis-free. It was considerably greater than the 18% (9 out of 50) in a previous control cohort (P<0.001, Fisher’s exact test). There were 8 major adverse events (including one death) reported, none of which were determined to be certainly or potentially connected to the study medication. The use of imlifidase was related to a superior outcome in the pilot investigation compared to previous publications, with no serious safety problems, but the findings needed to be verified in a randomized controlled trial.