Journal article
NI-0801, an anti-chemokine (C-X-C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid
- Abstract:
- 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).
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 516.7KB, Terms of use)
-
- Publisher copy:
- 10.1002/hep4.1170
Authors
- Publisher:
- Wiley
- Journal:
- Hepatology Communications More from this journal
- Volume:
- 2
- Issue:
- 5
- Pages:
- 492-503
- Publication date:
- 2018-03-23
- Acceptance date:
- 2018-02-22
- DOI:
- EISSN:
-
2471-254X
- Pmid:
-
29761166
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:853173
- UUID:
-
uuid:91816844-45cf-4919-979e-1d955eba7e86
- Local pid:
-
pubs:853173
- Source identifiers:
-
853173
- Deposit date:
-
2019-01-30
Terms of use
- Copyright holder:
- de Graaf et al
- Copyright date:
- 2018
- Notes:
- © 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
If you are the owner of this record, you can report an update to it here: Report update to this record