A randomized, placebo-controlled, single ascending-dose study to assess the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tralokinumab in Japanese healthy volunteers

摘要

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. Csubmax/sub, AUCsub(0–t)/sub, and AUCsub(0–inf)/sub increased in a dose-proportional manner, and mean tsub1/2/sub 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.