Nebokitug, an Anti-chemokine (C-C Motif) Ligand 24 Monoclonal Antibody, in Patients With Primary Sclerosing Cholangitis: A Phase 2 Study.
Christopher L Bowlus, Douglas Thorburn, Stephen T Barclay et al.
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In 30 seconds
SPRING was a multicentre, randomised, double-blind, placebo-controlled phase 2 trial of intravenous nebokitug in patients with large-duct primary sclerosing cholangitis (PSC). Seventy-six patients received nebokitug or placebo every 3 weeks for 15 weeks; eligible participants could continue nebokitug in an open-label extension for a total of 48 weeks. Adverse-event frequency and severity were similar between groups, and the overall treatment population had no significant changes in liver tests, enhanced liver fibrosis scores, or liver stiffness. In a prespecified subgroup with moderate/advanced fibrosis (n = 35), nebokitug was associated with a significant reduction in liver stiffness.
Key findings
- Among 76 treated patients, treatment-emergent adverse-event frequency and severity were similar with nebokitug and placebo.
- No significant week-15 changes in liver tests, ELF scores, or liver stiffness measurements were observed in the overall treatment population.
- In the prespecified moderate/advanced fibrosis subgroup (n = 35), nebokitug treatment was associated with a significant reduction in liver stiffness.
- Nebokitug was reported as well tolerated through 48 weeks, with no new safety signal in the open-label extension.
Why it matters
PSC has limited treatment options, and this trial assessed both safety and potential biological activity of a targeted antibody. The overall population showed no significant changes in the reported liver measures, while a prespecified subgroup with more advanced fibrosis had reduced liver stiffness. This subgroup result may inform further study, but does not establish clinical benefit.
What to keep in mind
The double-blind treatment period lasted 15 weeks, and the reported liver-measure findings were not significant in the overall treatment population. The subgroup result concerns liver stiffness, a measured biomarker.