Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy

Matthew Baker, Yashaar Chaichian, Mark Genovese, Vimal Derebail, Panduranga Rao, Winn Chatham, Michael Bubb, Sam Lim, Hooman Hajian, Oksana Gurtovaya, Uptal Patel, James Tumlin, Matthew Baker, Yashaar Chaichian, Mark Genovese, Vimal Derebail, Panduranga Rao, Winn Chatham, Michael Bubb, Sam Lim, Hooman Hajian, Oksana Gurtovaya, Uptal Patel, James Tumlin

Abstract

Objectives: Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.

Methods: This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16.

Results: Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib.

Conclusion: The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.

Trial registration number: NCT03285711.

Keywords: lupus erythematosus; lupus nephritis; systemic; therapeutics.

Conflict of interest statement

Competing interests: MBaker reports fees from Gilead unrelated to this study; MG, HH, OG, UP report employment and stock from Gilead Sciences.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Disposition of subjects.
Figure 2
Figure 2
Median per cent change in 24-hour urine protein.
Figure 3
Figure 3
Patient-level changes in three different urine protein measures.

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