Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, Following Intravenous or Subcutaneous Administration in Healthy Subjects.

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Khalilieh S, Hodsman P, Xu C, Tzontcheva A, Glasgow S, Montgomery D

Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, Following Intravenous or Subcutaneous Administration in Healthy Subjects.

Basic Clin Pharmacol Toxicol. 2018 Mar 6. doi: 10.1111/bcpt.13001.

PubMed ID
29510001 [ View in PubMed
]
Abstract

Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function, is under investigation for treatment of moderate-to-severe chronic plaque psoriasis. The objective of this analysis was to assess the pharmacokinetics (PK), bioavailability and safety/tolerability of single ascending doses of tildrakizumab following intravenous (IV) and subcutaneous (SC) dosing in healthy subjects. P05661 was a phase 1, single dose, randomized, placebo-controlled study of tildrakizumab IV doses of 0.1, 0.5, 3 and 10 mg/kg, or placebo. P05776 was a phase 1, single-dose, randomized, placebo-controlled study of tildrakizumab SC doses of 50 or 200 mg, or placebo. Following either single IV or SC dosing, tildrakizumab exhibited slow systemic clearance, limited volume of distribution and a long t(1/2) . Both the Cmax and the area under the curve (AUC) increased proportionally with doses from 0.1 mg/kg to 10 mg/kg, or 50 to 200 mg. The bioavailability of SC dosing was ~80% (90% CI: 62%-103%) for 50 mg and ~73% (90% CI: 46%-115%) for 200 mg, respectively, versus 0.5 mg/kg and 3 mg/kg IV. Across both studies, 6 of 43 evaluable subjects were positive for post-treatment antidrug antibodies; 2 of these were positive for neutralizing antibodies. Most adverse events (AEs) were mild; the most frequent AEs included upper respiratory tract infection and headache. Single doses of tildrakizumab 0.1, 0.5, 3 and 10 mg/kg administered IV or single doses of 50 mg and 200 mg administered SC were safe and well tolerated in healthy adult subjects. This article is protected by copyright. All rights reserved.

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