Randomized, double-blind, placebo-controlled phase 2a study assessing the efficacy and safety of felzartamab for IgA nephropathy

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT05065970.