Texas Arthritis Center, El Paso, TX, USA.
Complete Dermatology, Houston, TX, USA.
Adv Ther. 2022 Jun;39(6):2862-2872. doi: 10.1007/s12325-022-02126-0. Epub 2022 Apr 21.
Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.
Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh.
Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was - 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC, AUC, and C between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable.
Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation.
ClinicalTrials.gov identifier NCT03848403, NCT04259346.
皮下（SC）注射是一种常见的药物给药途径；然而，注射部位疼痛（ISP）可能会给患者带来负面体验。我们评估了无柠檬酸（CF）制剂 ixekizumab 的 ISP、生物等效性和整体安全性，ixekizumab 是一种高亲和力的单克隆抗体，选择性靶向白细胞介素-17A。
两项 1 期、单盲研究在健康参与者中进行。交叉研究 A（NCT03848403）通过视觉模拟评分法（VAS）评估注射时的疼痛强度。受试者（N=70）在开始时按 1:1:1 的比例随机分为三组，分别于第 1、8 和 15 天在腹部接受 1ml SC 注射。采用混合效应重复测量分析模型分析注射后时间的 VAS 评分。研究 B（NCT04259346）评估了 80mg 单剂量 CF 制剂与原商业制剂的生物等效性。受试者（N=245）按 1:1 的比例随机分为商业制剂或 CF 制剂组，均于腹部、手臂或大腿接受单次 SC 注射。
两项研究均达到了主要终点。在研究 A 中，商业制剂（n=61）和 CF 制剂（n=63）注射即刻后 VAS 评分的最小二乘均值（LSM）差值为-21.7（p<0.0001），表明 CF 制剂与较低程度的疼痛相关。在研究 B 中，CF 制剂的生物等效性得到确立，治疗间几何均数 AUC、AUC 和 C 的比值的 90%置信区间（CI）在预设的 0.8 和 1.25 范围内。除 CF 制剂的 ISP 较低外，整体安全性特征相当。
与原商业制剂相比，CF 制剂的 ixekizumab 被证明具有生物等效性，与较低的 ISP 相关，且在安全性特征方面没有其他显著差异。
ClinicalTrials.gov 标识符 NCT03848403、NCT04259346。
