{"title":"A Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of A140 Injection and Cetuximab (Erbitux®) in Healthy Chinese Male Subjects","authors":"Jia Xu, Junyou Ge, Yaling Li, Shulin Liu, Sicong Li, Jing Si, Juncheng Liu, Xiaoxue Zhu, Yanhua Ding","doi":"10.1007/s12325-025-03193-9","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>This study aimed to compare the pharmacokinetic (PK) profiles, safety, and immunogenicity of the proposed A140 with those of cetuximab (Erbitux<sup>®</sup>) in healthy Chinese male subjects.</p><h3>Methods</h3><p>We conducted a randomized, single-dose, double-blind, parallel-controlled phase I study in which 82 healthy subjects were randomized equally into the A140 group and the cetuximab group. Both the test and comparator drug were administered as a single intravenous (IV) dose of 250 mg/m<sup>2</sup>. Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the A140 to cetuximab for area under the concentration–time curve from time zero to the last measurable concentration (AUC<sub>0–<i>t</i></sub>) were within the predefined bioequivalence range of 80–125%.</p><h3>Results</h3><p>The results showed that the 90% CI of the GMR for PK parameters (AUC<sub>0–<i>t</i></sub>, AUC<sub>0–∞</sub>, <i>C</i><sub>max</sub>) between the A140 and cetuximab groups were all within the predefined equivalent interval of 80–125%. Furthermore, the types of treatment-related adverse events were similar between the two groups, with an incidence of 100%. However, approximately 80% of these events belonged to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2. Anti-drug antibody (ADA) profiles were comparable between the A140 and the cetuximab group.</p><h3>Conclusion</h3><p>A140 demonstrated similar PK to cetuximab and comparable safety and immunogenicity in healthy Chinese male subjects.</p><h3>Trial Registration</h3><p>CTR20182229 (https://www.chinadrugtrials.org.cn/).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 6","pages":"2797 - 2807"},"PeriodicalIF":3.4000,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12325-025-03193-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
This study aimed to compare the pharmacokinetic (PK) profiles, safety, and immunogenicity of the proposed A140 with those of cetuximab (Erbitux®) in healthy Chinese male subjects.
Methods
We conducted a randomized, single-dose, double-blind, parallel-controlled phase I study in which 82 healthy subjects were randomized equally into the A140 group and the cetuximab group. Both the test and comparator drug were administered as a single intravenous (IV) dose of 250 mg/m2. Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the A140 to cetuximab for area under the concentration–time curve from time zero to the last measurable concentration (AUC0–t) were within the predefined bioequivalence range of 80–125%.
Results
The results showed that the 90% CI of the GMR for PK parameters (AUC0–t, AUC0–∞, Cmax) between the A140 and cetuximab groups were all within the predefined equivalent interval of 80–125%. Furthermore, the types of treatment-related adverse events were similar between the two groups, with an incidence of 100%. However, approximately 80% of these events belonged to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2. Anti-drug antibody (ADA) profiles were comparable between the A140 and the cetuximab group.
Conclusion
A140 demonstrated similar PK to cetuximab and comparable safety and immunogenicity in healthy Chinese male subjects.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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