Background and Objective 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. Methods 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 (Cmax) 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. Results 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 Cmax, AUC from time zero extrapolated to infinity (AUC∞), and AUC from time zero to the time of the last quantifiable concentration (AUCt), 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 Cmax, AUC∞, and AUCt, 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 Cmax, AUC∞, and AUCt, respectively. Lastly, the geometric LSM ratios (90% CI) of treatment C versus D for Cmax, AUC∞, and AUCt 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. Conclusions 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. ClinicalTrials.gov NCT05337345.

Pharmacokinetic Characterization of Cendakimab Administered with Different Devices and at Different Injection Sites in Healthy Participants

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发表日期：

2025年5月15日

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Peijin Zhang,
Claudia H. M. C. De Oliveira,
Kyungha Yu,
Shenita Basdeo,
Christina M. Charriez,
Mary Syto,
Mark Thomas,
Bindu Murthy

摘要

Background and Objective

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.

Methods

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_max) 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.

Results

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_max, AUC from time zero extrapolated to infinity (AUC_∞), and AUC from time zero to the time of the last quantifiable concentration (AUC_t), 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_max, AUC_∞, and AUC_t, 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_max, AUC_∞, and AUC_t, respectively. Lastly, the geometric LSM ratios (90% CI) of treatment C versus D for C_max, AUC_∞, and AUC_t 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.

Conclusions

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.

ClinicalTrials.gov

NCT05337345.