Tralokinumab is a human
monoclonal antibody in clinical development for
asthma and
atopic dermatitis that specifically neutralizes
interleukin-13. This phase I, single-blind, randomized, placebo-controlled, single ascending-dose study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of subcutaneous
tralokinumab (150, 300, or 600 mg) in thirty healthy Japanese adults. The most frequent treatment-emergent adverse event (TEAE) in all treatment groups was injection-site
pain. The frequency and severity of TEAEs was similar across
tralokinumab doses. Cmax, AUC(0-t), and AUC(0-inf) increased in a dose-proportional manner, and mean t1/2 ranged from 20 to 25 days. No anti-drug
antibodies were detected. A post-hoc pooled population PK modeling analysis, incorporating PK data from this study, demonstrated that Japanese individuals had greater systemic exposure to
tralokinumab than non-Japanese individuals. This difference was not clinically relevant and was primarily due to differences in
body weight, with lower
body weight associated with greater PK exposure. Japanese ethnicity was not a significant predictor of
tralokinumab PK. This study indicates that single-dose subcutaneous administration of
tralokinumab 150-600 mg was well tolerated in Japanese healthy volunteers, and supports the 300 mg dose selection for Japanese patients with
asthma in ongoing clinical trials.