Pharmacokinetics, Safety, and Immunogenicity of Intravenous and Subcutaneous Single-Dose QX002N Injection in Healthy Subjects: A Randomized, Open, Parallel, Single-Center, Phase I Study.
IF 2.9
3区 医学
Q2 RHEUMATOLOGY
引用次数: 0
Abstract
Introduction: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies.
Methods: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay.
Results: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (Cmax) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%.
Conclusions: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects.
Trial registration: www.chinadrugtirals.org.cn , CTR20220430.
健康受试者静脉注射和皮下注射单剂量 QX002N 的药代动力学、安全性和免疫原性：一项随机、开放、平行、单中心 I 期研究。
导言：白细胞介素-17A（IL-17A）在强直性脊柱炎（AS）的发病机制中起着至关重要的作用，但并非所有患者都对传统的IL-17A抗体治疗有反应。QX002N注射液作为一种新的靶向IL-17A的单克隆抗体，已显示出治疗强直性脊柱炎的潜力，为对现有疗法反应不佳的患者提供了一种新的治疗选择：方法：本研究采用随机、开放、平行、单中心、I期研究方法，评估中国健康志愿者静脉注射（IV）或皮下注射（SC）单剂量QX002N注射液的药代动力学、安全性和免疫原性。在规定的时间间隔采集血样，然后用酶联免疫吸附试验分析血清中 QX002N 的浓度：结果：药物浓度-时间数据的药代动力学分析表明，观察到的 QX002N 平均最大血清浓度（Cmax）分别为 110 微克/毫升和 33.9 微克/毫升。从 0 到最后一次可定量的药物浓度时间曲线下的平均面积（AUClast）分别为 52,656 微克-小时/毫升和 36,269 微克-小时/毫升，从 0 到无穷大的药物浓度时间曲线下的平均面积（AUCinf）分别为 54,867 微克-小时/毫升和 38,194 微克-小时/毫升。QX002N经皮下注射后的绝对生物利用度为69.6%：本研究对免疫原性进行了评估，所有受试者的抗药抗体（ADA）均为阴性，这意味着没有受试者对QX002N产生免疫原性。所有结果都证明了 QX002N 注射剂的安全性，健康受试者静脉注射或皮下注射后的安全性令人满意。试验注册：www.chinadrugtirals.org.cn , CTR20220430。
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来源期刊
Rheumatology and Therapy
RHEUMATOLOGY-
CiteScore
6.00
自引率
5.30%
发文量
91
审稿时长
6 weeks
期刊介绍：
Aims and Scope
Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication 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 rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and 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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The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies
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The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies.
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