Randomized, Double-Blind, Placebo-Controlled Phase 2a Study Assessing the Efficacy and Safety of Felzartamab for IgA Nephropathy

<h4>Introduction</h4>Felzartamab is a fully human anti-CD38 monoclonal antibody under investigation for treatment of IgA nephropathy (IgAN). IGNAZ (NCT05065970) is a randomized, double blind, placebo-controlled Phase 2a study that assessed the efficacy and safety of felzartamab in 54 patients with biopsy-confirmed IgAN despite maximal renin angiotensin system blockade.<h4>Methods</h4>In Part 1, patients were randomized in the 6-month treatment period to receive intravenous placebo (12 patients) or felzartamab in three arms: two doses in 15 days (2-dose, 12 patients), five doses in 2 months (5-dose, 11 patients), or nine doses in five months (9-dose, 13 patients). In Part 2, six Japanese patients received the felzartamab 9-dose schedule open-label. Follow-up in Parts 1 and 2 was 24 and 12 months, respectively, after the first dose. The primary endpoint was change in proteinuria (urine protein to creatinine ratio [UPCR]) at nine months.<h4>Results</h4>Treatment with felzartamab versus placebo led to rapid (within 3-6 months) reduction in least-squares mean UPCR sustained at nine months (placebo, -5.7%; 2-dose, -12.5%; 5-dose, -12.8%; 9-dose, -29.5%; Part 2, -44.8%) and at 18 months after ending treatment (24 months), particularly in the 9-dose arm (-44.5%). Mean decreases in estimated glomerular filtration rate were lower with felzartamab than with placebo through 24 months in Part 1 and 12 months in Part 2. Felzartamab safety was consistent with prior observations; adverse events were predominantly grade 1 or 2.<h4>Conclusions</h4>Our study shows treatment with felzartamab results in sustained reduction of proteinuria, suggesting disease improvement. Further evidence is needed to understand the impact of felzartamab on preservation of kidney function in high-risk patients with IgAN.<p></p>