Clazakizumab improves albumin and inflammation in participants undergoing haemodialysis

Clazakizumab, a monoclonal antibody targeting IL-6, reduced inflammatory marker levels and increased serum albumin with manageable safety in participants with atherosclerotic cardiovascular disease receiving haemodialysis, according to phase 2b data.

The POSIBIL₆ESKD trial (NCT05485961) is a phase 2b/3 trial enrolling participants with a history of atherosclerotic cardiovascular disease, with/without diabetes and a hs-CRP >2 mg/L who are receiving maintenance dialysis. In the presented phase 2b dose-ranging trial part, participants were randomised 1:1:1:1 to 2.5, 5, or 10 mg IV clazakizumab every 4 weeks, or placebo. The primary endpoint was the change from baseline at week 12 in hs-CRP. In total, 127 participants were included [1].

All 3 clazakizumab doses decreased mean hs-CRP levels which was sustained over time. After 12 weeks, the geometric mean change in hs-CRP was -86%, -90% and -92% with clazakinumab 2.5, 5, and 10 mg, respectively, while the placebo group led to a 19% increase in hs-CRP. Twelve weeks of clazakizumab increased serum albumin by 0.28, 0.25, and 0.21 g/dL (2.5, 5, and 10 mg, respectively), compared with a 0.04 g/dL increase with placebo. “In clinical practice, I very rarely see an increase of serum albumin much greater than 0.2 or 0.3 g/dL, especially considering the time course of 6 months, let alone 3 months”, highlighted Prof. Glenn Chertow (Stanford University School of Medicine, Stanford, CA, USA), placing the findings into context. In terms of safety, clazakinumab led to 2 episodes of grade 3 neutropenia and 2 episodes of thrombocytopenia which were managed by withholding the investigational treatment. Furthermore, serious infections were observed in all clazakizumab groups and incidences increased with increasing doses.

“Low-dose clazakizumab reduced inflammatory markers associated with cardiovascular disease and increased serum albumin in a small cohort of participants receiving haemodialysis with background inflammation”, summarised Prof. Chertow. “A phase 3 trial using 5 mg clazakizumab is underway.”

1. Chertow G, et al. A Phase 2b/3 trial assessing IL-6 inhibition with clazakizumab in patients with cardiovascular disease or diabetes on dialysis: Results from Phase 2b. Abstract #7, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024