Peijin Zhang, Claudia H M C De Oliveira, Kyungha Yu, Shenita Basdeo, Christina M Charriez, Mary Syto, Mark Thomas, Bindu Murthy
{"title":"健达单抗在健康受试者中不同装置和不同注射部位的药代动力学特征","authors":"Peijin Zhang, Claudia H M C De Oliveira, Kyungha Yu, Shenita Basdeo, Christina M Charriez, Mary Syto, Mark Thomas, Bindu Murthy","doi":"10.1007/s13318-025-00949-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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<sub>max</sub>) 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.</p><p><strong>Results: </strong>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<sub>max</sub>, AUC from time zero extrapolated to infinity (AUC<sub>∞</sub>), and AUC from time zero to the time of the last quantifiable concentration (AUC<sub>t</sub>), 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<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub>, 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<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub>, respectively. Lastly, the geometric LSM ratios (90% CI) of treatment C versus D for C<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub> 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinicaltrials: </strong>GOV: NCT05337345.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Characterization of Cendakimab Administered with Different Devices and at Different Injection Sites in Healthy Participants.\",\"authors\":\"Peijin Zhang, Claudia H M C De Oliveira, Kyungha Yu, Shenita Basdeo, Christina M Charriez, Mary Syto, Mark Thomas, Bindu Murthy\",\"doi\":\"10.1007/s13318-025-00949-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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<sub>max</sub>) 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.</p><p><strong>Results: </strong>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<sub>max</sub>, AUC from time zero extrapolated to infinity (AUC<sub>∞</sub>), and AUC from time zero to the time of the last quantifiable concentration (AUC<sub>t</sub>), 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<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub>, 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<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub>, respectively. Lastly, the geometric LSM ratios (90% CI) of treatment C versus D for C<sub>max</sub>, AUC<sub>∞</sub>, and AUC<sub>t</sub> 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinicaltrials: </strong>GOV: NCT05337345.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-025-00949-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-025-00949-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetic Characterization of Cendakimab Administered with Different Devices and at Different Injection Sites in Healthy Participants.
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.
期刊介绍：
Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences.
Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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