Evaluation of Pharmacokinetics of Lebrikizumab in Healthy Individuals After Subcutaneous Administration Using a Prefilled Syringe or Autoinjector in a Phase 1 Randomized Study

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2025-01-01 DOI:10.1016/j.clinthera.2024.10.016

Amita Datta-Mannan PhD , Brian Moser MS , Wen Xu PhD , Kimberley Jackson PhD , Jennifer Witcher PhD , April W. Armstrong MD MPH , Andrew Blauvelt MD, MBA , Peter A. Lio MD

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引用次数: 0

Abstract

Purpose

Lebrikizumab is a novel, high-affinity immunoglobulin G4 monoclonal antibody that targets interleukin-13, a central mediator in atopic dermatitis (AD). In previous studies in patients with moderate-to-severe AD, lebrikizumab, administered subcutaneously via a prefilled syringe with a needle safety device (PFS-NSD), demonstrated rapid and durable dose-dependent efficacy. We assessed the pharmacokinetics and safety of lebrikizumab using either a PFS-NSD or an investigational autoinjector. Such devices have been developed to make self-injection easier for patients, thus increasing adherence over long treatment durations.

Methods

The current study compared the pharmacokinetics and safety of 250 mg lebrikizumab (2 mL of a 125-mg/mL solution) administered subcutaneously at 1 of 3 different injection sites (abdomen, arm, or thigh) in 241 healthy participants using either a PFS-NSD (N = 122) or an investigational autoinjector (N = 119).

Findings

Statistical analysis demonstrated 2-mL (125 mg/mL) lebrikizumab autoinjector was bioequivalent to 2-mL (125 mg/mL) lebrikizumab PFS-NSD as 90% CIs of the geometric least squares means ratios for lebrikizumab AUC_(0-tlast), AUC_(0-∞), and C_max were all completely contained within the prespecified confidence limits of 0.80 and 1.25. Injection-site location did not appear to impact lebrikizumab systemic exposure for either device. Lebrikizumab was well tolerated with no SAEs reported after PFS-NSD or autoinjector administration.

Implications

Bioequivalence was demonstrated between 250 mg lebrikizumab 2-mL autoinjector and prefilled syringe devices, showing both devices to be suitable options for administering lebrikizumab.

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在一项1期随机研究中，使用预充注射器或自动注射器皮下给药后，来布单抗在健康个体中的药代动力学评估

目的：Lebrikizumab是一种新型的高亲和力免疫球蛋白G4单克隆抗体，靶向白介素-13，白介素-13是特应性皮炎（AD）的中心介质。在先前针对中重度AD患者的研究中，lebrikizumab通过带针头安全装置（PFS-NSD）的预填充注射器皮下给药，显示出快速和持久的剂量依赖性疗效。我们使用PFS-NSD或研究性自动注射器评估lebrikizumab的药代动力学和安全性。这种装置的发展使患者自我注射更容易，从而增加了长期治疗持续时间的依从性。方法：目前的研究比较了241名健康参与者使用PFS-NSD （N = 122）或研究性自动注射器（N = 119）在3个不同注射部位（腹部、手臂或大腿）中的1个皮下给药250mg lebrikizumab （2ml 125 mg/mL溶液）的药代动力学和安全性。结果：统计分析表明，2-mL (125 mg/mL) lebrikizumab自动注射器与2-mL (125 mg/mL) lebrikizumab PFS-NSD生物等效，lebrikizumab AUC(0-tlast)， AUC（0-∞）和Cmax的几何最小二乘平均比的90% CIs都完全包含在预设的置信范围内0.80和1.25。注射部位的位置似乎对两种装置的来布单抗全身暴露没有影响。Lebrikizumab耐受性良好，在PFS-NSD或自动注射器给药后没有报告sae。意义：250mg lebrikizumab 2ml自动注射器和预充注射器装置之间的生物等效性被证明，表明这两种装置都是给药lebrikizumab的合适选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.