Safety and pharmacokinetics of olokizumab, an anti-IL-6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study
- PMID: 27129012
- DOI: 10.1002/cpdd.121
Safety and pharmacokinetics of olokizumab, an anti-IL-6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study
Abstract
Interleukin-6 (IL-6) is implicated in the pathophysiology of several inflammatory conditions. Olokizumab, a humanized anti-IL-6 monoclonal antibody, selectively blocks the final assembly of the IL-6 signaling complex. A randomized, double-blind, placebo-controlled, phase I dose-escalation study assessed the safety and tolerability of escalating single doses of olokizumab administered intravenously (iv) or subcutaneously (sc) to 67 healthy male volunteers. The pharmacokinetics, pharmacodynamics and immunogenicity of olokizumab were also assessed. Olokizumab was tolerated at doses up to 3.0 mg/kg sc and 10.0 mg/kg iv; the maximum tolerated dose was not reached. No serious adverse events or withdrawals as a result of treatment-emergent adverse events were reported. Pharmacokinetic analysis showed that both maximum serum concentration and area under the concentration-time curve increased linearly with increasing dose. Mean terminal half-life was 31.5 days (standard deviation 12.4 days). The bioavailability of the sc doses ranged from 84.2% to 92.5%. Rapid decreases in C-reactive protein concentrations were observed, with no dose dependency.
Keywords: anti-IL-6; first in human; olokizumab; pharmacokinetics; safety.
© 2014 The Authors. Clinical Pharmacology in Drug Development Published by WileyPeriodicals, Inc. on behalf of The American College of Clinical Pharmacology.
Similar articles
-
The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study.Br J Dermatol. 2016 Feb;174(2):296-304. doi: 10.1111/bjd.14207. Epub 2015 Dec 19. Br J Dermatol. 2016. PMID: 26409172 Clinical Trial.
-
First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis.Eur J Clin Pharmacol. 2016 Nov;72(11):1303-1310. doi: 10.1007/s00228-016-2110-5. Epub 2016 Aug 11. Eur J Clin Pharmacol. 2016. PMID: 27515978 Clinical Trial.
-
Vedolizumab Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability Following Administration of a Single, Ascending, Intravenous Dose to Healthy Volunteers.Clin Drug Investig. 2016 Nov;36(11):913-923. doi: 10.1007/s40261-016-0437-4. Clin Drug Investig. 2016. PMID: 27422740 Clinical Trial.
-
A Double-Blind, Phase I, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BOS161721 in Healthy Subjects.Clin Transl Sci. 2020 Mar;13(2):337-344. doi: 10.1111/cts.12715. Epub 2019 Nov 29. Clin Transl Sci. 2020. PMID: 31664766 Free PMC article. Clinical Trial.
-
Safety and tolerability of a humanized rabbit monoclonal antibody (SSS07) in healthy adults: Randomized double-blind placebo-controlled single ascending dose trial.Int Immunopharmacol. 2021 Feb;91:107263. doi: 10.1016/j.intimp.2020.107263. Epub 2020 Dec 28. Int Immunopharmacol. 2021. PMID: 33383447 Clinical Trial.
Cited by
-
Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review).Exp Ther Med. 2021 Mar;21(3):263. doi: 10.3892/etm.2021.9693. Epub 2021 Jan 25. Exp Ther Med. 2021. PMID: 33603870 Free PMC article. Review.
-
Inter-Antibody Variability in the Clinical Pharmacokinetics of Monoclonal Antibodies Characterized Using Population Physiologically Based Pharmacokinetic Modeling.Antibodies (Basel). 2024 Jul 9;13(3):54. doi: 10.3390/antib13030054. Antibodies (Basel). 2024. PMID: 39051330 Free PMC article.
-
Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis.J Pers Med. 2022 Apr 15;12(4):641. doi: 10.3390/jpm12040641. J Pers Med. 2022. PMID: 35455757 Free PMC article.
-
Repurpose but also (nano)-reformulate! The potential role of nanomedicine in the battle against SARS-CoV2.J Control Release. 2021 Sep 10;337:258-284. doi: 10.1016/j.jconrel.2021.07.028. Epub 2021 Jul 20. J Control Release. 2021. PMID: 34293319 Free PMC article. Review.
-
Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.J Transl Med. 2024 Apr 30;22(1):402. doi: 10.1186/s12967-024-05205-8. J Transl Med. 2024. PMID: 38689325 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
