Open AccessNI‐0801, an anti‐chemokine (C‐X‐C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid
Author(s) -
de Graaf Kathy L.,
Lapeyre Geneviève,
Guilhot Florence,
Ferlin Walter,
Curbishley Stuart M.,
Carbone Marco,
Richardson Paul,
Moreea Sulleman,
McCune C. Anne,
Ryder Stephen D.,
Chapman Roger W.,
Floreani Annarosa,
Jones David E.,
de Min Cristina,
Adams David H.,
Invernizzi Pietro
Publication year - 2018
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1170
Subject(s) - medicine , gastroenterology , adverse effect , pharmacokinetics , ursodeoxycholic acid , hepatology , liver function , pharmacodynamics , cxcl10 , chemokine , inflammation
NI‐0801 is a fully human monoclonal antibody against chemokine (C‐X‐C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI‐0801 was assessed in patients with primary biliary cholangitis. In this open‐label phase 2a study, patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid received six consecutive intravenous administrations of NI‐0801 (10 mg/kg) every 2 weeks. Patients were followed up for 3 months after the last infusion. Liver function tests, safety assessments, as well as pharmacokinetic and pharmacodynamic parameters were evaluated at different time points throughout the dosing period and the safety follow‐up period. Twenty‐nine patients were enrolled in the study and were treated with NI‐0801. The most frequently reported adverse events included headaches (52%), pruritus (34%), fatigue (24%), and diarrhea (21%). No study drug‐related serious adverse events were reported. NI‐0801 administration did not lead to a significant reduction in any of the liver function tests assessed at the end of the treatment period (i.e., 2 weeks after final NI‐0801 administration) compared to baseline. Conclusion: Despite clear pharmacologic responses in the blood, no therapeutic benefit of multiple administrations of NI‐0801 could be demonstrated. The high production rate of CXCL10 makes it difficult to achieve drug levels that lead to sustained neutralization of the chemokine, thus limiting its targetability. ( Hepatology Communications 2018;2:492‐503)