Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study
Background Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).Methods This was a...
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BMJ Publishing Group
2025-08-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/11/3/e005557.full |
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| author | Renaud Felten Nan Shen Julia Weinmann-Menke Ana Malvar Peter Gergely Tamas Shisha Carole Sips André Serra-Roma Markus Weiss Rambabu Danekula Jan Rohr |
| author_facet | Renaud Felten Nan Shen Julia Weinmann-Menke Ana Malvar Peter Gergely Tamas Shisha Carole Sips André Serra-Roma Markus Weiss Rambabu Danekula Jan Rohr |
| author_sort | Renaud Felten |
| collection | DOAJ |
| description | Background Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).Methods This was a phase II, randomised, double-blind, placebo-controlled, multicentre study including patients with a diagnosis of systemic lupus erythematosus with active LN. Patients were randomly assigned (2:1) to receive either intravenous iscalimab (10 mg/kg) or placebo for 24 weeks on top of SoC for LN. The primary efficacy endpoint was the ratio from baseline in urinary protein-to-creatinine ratio (UPCR) at week 24. Safety assessments included adverse events (AEs) and serious AEs (SAEs) during treatment and follow-up up to 49 weeks.Findings Of the 57 patients (iscalimab, n=39; placebo, n=18) randomised, 31 (54.4%) completed the study. The primary efficacy endpoint was met: at week 24, the relative improvement from baseline in proteinuria (UPCR) was 63.1% and 36.3% in the iscalimab and placebo arms, respectively. UPCR to baseline at week 24 showed a statistically significant reduction of 42.1% in the iscalimab versus placebo arm. Most AEs were of mild to moderate severity in both treatment arms. Overall, seven SAEs were reported in six patients (15.4%) in the iscalimab arm versus four in three patients (16.7%) in the placebo arm.Interpretation Iscalimab showed a significant improvement in proteinuria (UPCR) in patients with active LN. Iscalimab was generally well tolerated with the exception of a few severe infections and one case of macrophage-activation syndrome in immunosuppressed and comorbid patients.Trial registration number NCT03610516. |
| format | Article |
| id | doaj-art-e17706e3e0954a379fdee56a70bce3d3 |
| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj-art-e17706e3e0954a379fdee56a70bce3d32025-08-20T03:41:36ZengBMJ Publishing GroupRMD Open2056-59332025-08-0111310.1136/rmdopen-2025-005557Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II studyRenaud Felten0Nan Shen1Julia Weinmann-Menke2Ana Malvar3Peter Gergely4Tamas Shisha5Carole Sips6André Serra-Roma7Markus Weiss8Rambabu Danekula9Jan Rohr10Novartis Pharma AG, Basel, SwitzerlandDepartment of Rheumatology, Shanghai JiaoTong University School of Medicine, Shanghai, ChinaDepartment of Nephrology, Rheumatology and Kidney Transplantation, University Medical Center of the Johannes Gutenberg University, Mainz, GermanyNephrology Unit, Hospital General de Agudos Juan A Fernández, Buenos Aires, ArgentinaNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandBackground Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).Methods This was a phase II, randomised, double-blind, placebo-controlled, multicentre study including patients with a diagnosis of systemic lupus erythematosus with active LN. Patients were randomly assigned (2:1) to receive either intravenous iscalimab (10 mg/kg) or placebo for 24 weeks on top of SoC for LN. The primary efficacy endpoint was the ratio from baseline in urinary protein-to-creatinine ratio (UPCR) at week 24. Safety assessments included adverse events (AEs) and serious AEs (SAEs) during treatment and follow-up up to 49 weeks.Findings Of the 57 patients (iscalimab, n=39; placebo, n=18) randomised, 31 (54.4%) completed the study. The primary efficacy endpoint was met: at week 24, the relative improvement from baseline in proteinuria (UPCR) was 63.1% and 36.3% in the iscalimab and placebo arms, respectively. UPCR to baseline at week 24 showed a statistically significant reduction of 42.1% in the iscalimab versus placebo arm. Most AEs were of mild to moderate severity in both treatment arms. Overall, seven SAEs were reported in six patients (15.4%) in the iscalimab arm versus four in three patients (16.7%) in the placebo arm.Interpretation Iscalimab showed a significant improvement in proteinuria (UPCR) in patients with active LN. Iscalimab was generally well tolerated with the exception of a few severe infections and one case of macrophage-activation syndrome in immunosuppressed and comorbid patients.Trial registration number NCT03610516.https://rmdopen.bmj.com/content/11/3/e005557.full |
| spellingShingle | Renaud Felten Nan Shen Julia Weinmann-Menke Ana Malvar Peter Gergely Tamas Shisha Carole Sips André Serra-Roma Markus Weiss Rambabu Danekula Jan Rohr Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study RMD Open |
| title | Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study |
| title_full | Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study |
| title_fullStr | Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study |
| title_full_unstemmed | Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study |
| title_short | Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study |
| title_sort | efficacy pharmacokinetics and safety of iscalimab cfz533 in patients with proliferative lupus nephritis a randomised double blind placebo controlled phase ii study |
| url | https://rmdopen.bmj.com/content/11/3/e005557.full |
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