{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, Shanghai JiaoTong University School of Medicine, Shanghai, China"
      ],
      "name": "Nan Shen"
    },
    {
      "affiliations": [
        "Department of Nephrology, Rheumatology and Kidney Transplantation, University Medical Center of the Johannes Gutenberg University, Mainz, Germany"
      ],
      "name": "Julia Weinmann-Menke"
    },
    {
      "affiliations": [
        "Nephrology Unit, Hospital General de Agudos Juan A Fernández, Buenos Aires, Argentina"
      ],
      "name": "Ana Malvar"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "André Serra-Roma"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Markus Weiss"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Rambabu Danekula"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Carole Sips"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Jan Rohr"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Renaud Felten"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Peter Gergely"
    },
    {
      "affiliations": [
        "Novartis Pharma AG, Basel, Switzerland"
      ],
      "name": "Tamas Shisha"
    }
  ],
  "title": "Efficacy, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study",
  "uid": "a3d54a5f-e96d-5d13-a590-9b829889b270"
}