A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers
| العنوان: | A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers |
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| المؤلفون: | Xiaojiao Li, Katherine Chai, Yanhua Ding, Min Wu, Jixuan Sun, Xiaodi Zhang, Chen Yu, Hongjie Qian, Xiaoxue Zhu |
| المصدر: | Cancer Chemotherapy and Pharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, China, Cancer Research, medicine.medical_specialty, Bevacizumab, Cmax, Phases of clinical research, Bioequivalence, Toxicology, Young Adult, Antineoplastic Agents, Immunological, Asian People, Double-Blind Method, Pharmacokinetics, Internal medicine, Humans, Medicine, media_common.cataloged_instance, Pharmacology (medical), European Union, European union, Infusions, Intravenous, Adverse effect, Biosimilar Pharmaceuticals, media_common, Pharmacology, business.industry, Biosimilar, Middle Aged, United States, Confidence interval, Therapeutic Equivalency, Oncology, Area Under Curve, Original Article, business, medicine.drug |
| الوصف: | Purpose To compare the pharmacokinetic profiles, safety and immunogenicity of proposed bevacizumab biosimilar HLX04 with reference bevacizumab in healthy Chinese males. Methods In this double-blind Phase 1 study, healthy volunteers (N = 208) were randomized 1:1:1:1 to a single 3 mg/kg intravenous infusion of HLX04 or reference bevacizumab sourced from the United States (bevacizumab-US), the European Union (bevacizumab-EU) or China (bevacizumab-CN). Co-primary endpoints were area under the serum concentration–time profile (AUC) from time zero extrapolated to infinity (AUC0–inf) and from zero to last quantifiable concentration (AUClast). Secondary endpoint was the maximum serum drug concentration (Cmax). Study participants were monitored for treatment-emergent adverse events (TEAEs) and samples were collected for anti-drug antibody (ADA) testing throughout the study. Results Pharmacokinetic parameters were similar across groups. The respective geometric least-squares mean ratios (GLSMR) of AUC0–inf, AUClast and Cmax were: 95.7%, 96.0% and 101.8% for HLX04 versus bevacizumab-US; 94.3%, 94.6% and 100.5% for HLX04 versus bevacizumab-EU; and 90.0%, 90.4% and 98.2% for HLX04 versus bevacizumab-CN. For all test-to-reference comparisons, two-sided 90% confidence intervals of GLSMR for AUC0–inf, AUClast and Cmax fell in the pre-specified bioequivalence range (80–125%). There were no notable differences in the frequency, nature and/or grade of TEAEs. No deaths were reported and no ADAs were detected during the study. Conclusion HLX04 had similar safety and pharmacokinetic profiles to reference bevacizumab in healthy Chinese males, supporting the confirmatory Phase 3 study investigating the efficacy and safety equivalence between HLX04 and bevacizumab in patients with metastatic colorectal cancer (NCT03511963). Clinical trial registration The study was registered with Clinicaltrials.gov, NCT03483649. |
| تدمد: | 1432-0843 0344-5704 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::727d2b14e50e3a02ef655e4aa4b3ac47 https://doi.org/10.1007/s00280-021-04297-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....727d2b14e50e3a02ef655e4aa4b3ac47 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320843 03445704 |
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