Zhang Peijin, De Oliveira Claudia H M C, Yu Kyungha, Basdeo Shenita, Charriez Christina M, Syto Mary, Thomas Mark, Murthy Bindu
Bristol Myers Squibb, Princeton, NJ, USA.
Eur J Drug Metab Pharmacokinet. 2025 May 15. doi: 10.1007/s13318-025-00949-0.
The cendakimab (CC-93538, previously RPC4046) phase 3 trial used prefilled syringes (PFS), while the intended commercial product is an autoinjector (AI). This study evaluated the pharmacokinetic (PK) comparability of cendakimab administration by PFS and AI, and at different injection sites.
This was a phase 1, single-center, randomized, open-label, single-dose, two-part parallel-group study (NCT05337345) in healthy adults. In part 1, participants were randomized 1:1 to receive cendakimab 360 mg subcutaneously in the abdomen by PFS (treatment A) or AI (treatment B). In part 2, participants were randomized to receive cendakimab 360 mg subcutaneously in either the upper arm (treatment C) or upper thigh area (treatment D) by AI. Analysis of covariance was used to compare the log-transformed area under the curve (AUC) and peak concentration (C) between PFS and AI devices. PK parameters based on cendakimab serum concentration were estimated using noncompartmental analysis and actual PK collection time. Immunogenicity was evaluated via measurement of antidrug antibody (ADA) titer over 105 (± 2) days after dosing; the impact of ADAs on the safety and PK of cendakimab was evaluated.
Overall, 64 and 40 healthy adults were dosed in parts 1 and 2, respectively. In part 1, the geometric least squares mean (LSM) ratios (90% CI) of treatment B versus A were contained within the generally accepted limit of 80-125%; 1.04 (0.90-1.20), 0.98 (0.87-1.12), and 0.99 (0.87-1.12) for C, AUC from time zero extrapolated to infinity (AUC), and AUC from time zero to the time of the last quantifiable concentration (AUC), respectively. The geometric LSM ratios (90% CI) of treatment C versus B were 1.21 (1.05-1.39), 1.21 (1.07-1.38), and 1.22 (1.08-1.38) for C, AUC, and AUC, respectively. The geometric LSM ratios (90% CI) of treatment D versus B were 1.23 (1.06-1.41), 1.26 (1.11-1.43), and 1.26 (1.11-1.42) for C, AUC, and AUC, respectively. Lastly, the geometric LSM ratios (90% CI) of treatment C versus D for C, AUC, and AUC were contained entirely within 80-125%. In part 1, 43.8% (n = 14) of participants receiving treatment A (PFS, abdomen) and 40.6% (n = 13) receiving treatment B (AI, abdomen) reported ≥ 1 adverse event (AE). In part 2, 35.0% (n = 7) of participants receiving either treatment C (AI, upper arm) or treatment D (AI, upper thigh) reported ≥ 1 AE. There were no serious/severe AEs and no discontinuations due to an AE.
PK parameters of cendakimab were comparable when using PFS or AI. Cendakimab exposures when administered in the arm or thigh resulted in similar exposure; both were ~ 20% higher than when administering in the abdomen. Both PFS and AI were well tolerated. ADA status did not impact the PK or safety of cendakimab.
GOV: NCT05337345.
塞达基单抗（CC - 93538，之前称为RPC4046）的3期试验使用预填充注射器（PFS），而预期的商业产品是自动注射器（AI）。本研究评估了通过PFS和AI给药以及在不同注射部位给药时塞达基单抗的药代动力学（PK）可比性。
这是一项在健康成年人中进行的1期、单中心、随机、开放标签、单剂量、两部分平行组研究（NCT05337345）。在第1部分中，参与者按1:1随机分组，通过PFS在腹部皮下注射360mg塞达基单抗（治疗A）或通过AI注射（治疗B）。在第2部分中，参与者随机分组，通过AI在上臂（治疗C）或大腿上部区域（治疗D）皮下注射360mg塞达基单抗。采用协方差分析比较PFS和AI装置之间对数转换后的曲线下面积（AUC）和峰浓度（C）。基于塞达基单抗血清浓度的PK参数使用非房室分析和实际PK采集时间进行估计。在给药后105（±2）天内通过测量抗药抗体（ADA）滴度评估免疫原性；评估ADA对塞达基单抗安全性和PK的影响。
总体而言，第1部分和第2部分分别有64名和40名健康成年人给药。在第1部分中，治疗B与治疗A的几何最小二乘均值（LSM）比值（90%CI）在普遍接受的80 - 125%范围内；C、从时间零点外推至无穷大的AUC（AUC）和从时间零点至最后可定量浓度时间的AUC（AUC）的比值分别为1.04（0.90 - 1.20）、0.98（0.87 - 1.12）和0.99（0.87 - 1.12）。治疗C与治疗B的几何LSM比值（90%CI），C、AUC和AUC分别为1.21（1.05 - 1.39）、1.21（1.07 - 1.38）和1.22（1.08 - 1.38）。治疗D与治疗B的几何LSM比值（90%CI），C、AUC和AUC分别为1.23（1.06 - 1.41）、1.26（1.11 - 1.43）和1.26（1.11 - 1.42）。最后，治疗C与治疗D的C、AUC和AUC的几何LSM比值（90%CI）完全在80 - 125%范围内。在第1部分中，接受治疗A（PFS，腹部）的参与者中有43.8%（n = 14）和接受治疗B（AI，腹部）的参与者中有40.6%（n = 13）报告了≥1次不良事件（AE）。在第
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