Randomized, double-blind, placebo-controlled phase 2a study assessing the efficacy and safety of felzartamab for IgA nephropathy
Kidney International, vol. 108, pp. 695–706
Abstract
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.
Authors 13
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Division of Nephrology and Cardiology, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany. Electronic address: jfloege@ukaachen.de
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Stanford Medicine · Stanford University
Affiliation as printed
Division of Nephrology, Department of Medicine, Stanford University, Stanford, California, USA
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Affiliation as printed
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
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Affiliation as printed
Biogen, South San Francisco, California, USA
Human Immunology Biosciences, Inc., a Biogen Company, South San Francisco, California, USA
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Affiliation as printed
Biogen, South San Francisco, California, USA
Human Immunology Biosciences, Inc., a Biogen Company, South San Francisco, California, USA
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Affiliation as printed
Biogen, South San Francisco, California, USA
Human Immunology Biosciences, Inc., a Biogen Company, South San Francisco, California, USA
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Affiliation as printed
Biogen, South San Francisco, California, USA
Human Immunology Biosciences, Inc., a Biogen Company, South San Francisco, California, USA
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Affiliation as printed
Biogen, South San Francisco, California, USA
Human Immunology Biosciences, Inc., a Biogen Company, South San Francisco, California, USA
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Affiliation as printed
MorphoSys GmbH, a Novartis Company, Planegg, Germany
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Affiliation as printed
MorphoSys GmbH, a Novartis Company, Planegg, Germany
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Affiliation as printed
MorphoSys GmbH, a Novartis Company, Planegg, Germany
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Affiliation as printed
MorphoSys GmbH, a Novartis Company, Planegg, Germany
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University of British Columbia
Affiliation as printed
Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
Cited by 30 stored of 30
Cited by patents worldwide 1 (Lens.org)
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ANTI-CD38 ANTIBODIES AND THEIR USESWO2026080575A1 2026-04-16 Pending