| Description: |
Background and Aims Most patients with IgA nephropathy (IgAN) will progress to kidney failure within 10-15 years of diagnosis. Sustained proteinuria is the best predictor of adverse long-term kidney outcomes and is a surrogate marker for efficacy. CD38+ plasma cells are likely the main source of pathogenic Gd-IgA1, and the related autoantibodies in IgAN. Felzartamab (felza; HIB202) is a recombinant purified human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to CD38 on plasma cells and is being studied across immune-mediated kidney diseases such as IgAN, Primary Membranous Nephropathy, Lupus Nephritis, and Antibody Mediated Rejection. The primary aims of the IGNAZ study were to assess: 1) efficacy of felza compared to placebo on urine protein:creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) change from baseline, and 2) the relationship between exposure, safety, and efficacy in each of 3 dose groups vs. placebo. Interim results with 15 months of follow-up from this 24-month trial are presented. Method In Part 1, 48 IgAN subjects were randomized in a 1:1:1:1 ratio across a placebo and 3 active arms in this multicenter, double-blind placebo-controlled, phase IIa trial. The M1, M2, and M3 active arms received 2 doses in 15 days, 5 doses in 2 months, and 9 doses in 5 months, respectively. In Part 2, 6 Japanese subjects received the M3 regimen, open-label, and have been followed for 9 months. Key inclusion criteria included ages 18-80 years, biopsy confirmed diagnosis of IgAN within the past 8 years, proteinuria at screening ≥1.0 g/d, eGFR ≥30 ml/min/1.73 m2 (by CKD-EPI), and background stable and maximally tolerated renin angiotensin system inhibitors. Results 48 randomized subjects were enrolled at 28 sites in the US and in 14 different countries in Europe and in Asia, of which 46 completed the treatment phase. Mean (SD) baseline characteristics (Parts 1 and 2 combined): age 41.6 (12.3) yrs, UPCR 1.67 (1.0) g/g, eGFR 74.6 (30.3) ml/min/1.73 m2. 67% of subjects were ... |