Nebokitug, an Anti-chemokine (C-C Motif) Ligand 24 Monoclonal Antibody, in Patients With Primary Sclerosing Cholangitis: A Phase 2 Study.

Abstract

Nebokitug (CM-101) is an antichemokine (C-C motif) ligand 24 monoclonal antibody with anti-inflammatory and antifibrotic properties. This phase 2 study evaluated the safety, tolerability, and biological activity of nebokitug in patients with primary sclerosing cholangitis (PSC). SPRING was a randomized, double-blind (DB), placebo-controlled phase 2 study in which patients with large duct PSC were randomized to receive IV nebokitug 10 mg/kg, 20 mg/kg, or placebo every 3 weeks for 15 weeks. The primary end point was safety and tolerability. Secondary end points included change from baseline to week 15 in liver blood tests, enhanced liver fibrosis (ELF) score, and liver stiffness measurements (LSM). Biological activity was explored in a prespecified subgroup with moderate/advanced fibrosis. Eligible patients who completed the 15-week DB period entered the open-label extension study to receive nebokitug for a total of 48 weeks. A total of 76 patients were enrolled and received at least 1 dose of nebokitug (n = 56) or placebo (n = 20). Frequency and severity of treatment-emergent adverse events were similar between the groups. No significant changes in liver tests, ELF scores, and LSM from baseline to week 15 were observed in the total treatment population. However, in the prespecified subgroup of patients with moderate/advanced fibrosis (n = 35), patients treated with nebokitug showed a significant reduction in LSM. Of the 54 patients eligible to participate, 50 enrolled in the OLE. Nebokitug continued to be well tolerated, and no new safety signal was observed. Nebokitug was well tolerated up to 48 weeks of treatment and demonstrated numerical biomarker improvements in patients with PSC, particularly in those with moderate/advanced fibrosis.