First-in-human study of two anti-SARS CoV-2 antibodies in health volunteers

项目摘要 2019年冠状病毒病（COVID-19）大流行目前正在困扰世界，没有已知的治愈方法， 预防除了健康后果外，人类活动的必要减少还导致 经济损失没有现代先例，特别是在发展中国家， 即使在大流行之前也不够。目前正在作出巨大努力研制疫苗， SARS-CoV-2和抗体很可能是必不可少的保护。 目前正在研究以来自康复个体的多克隆血浆形式的COVID-19抗体疗法。 作为一种治疗选择进行了探索，并已获得FDA的紧急使用授权（EUA）。 单克隆抗体可能被证明在预防人群中SARS-CoV-2感染方面特别有用 可能不会对疫苗接种产生保护性免疫应答的人（例如，高龄、免疫功能低下）， 用于发生严重COVID-19的高风险个体的暴露后预防。 C135和C144是特异性结合SARS-CoV-2刺突蛋白受体的重组全人源mAb 结合域（RBD），并在体外表现出针对SARS-CoV-2的出色中和活性。两个一氨基 已引入酸突变以延长半衰期并允许剂量节省。C135-LS和C144-LS 在几个相关的预防和治疗实验中， 预防和治疗实验中的动物模型。这些临床前数据支持临床评价 从SARS-CoV-2和加速病毒清除和疾病的解决在SARS-CoV-2感染的个人。 所提出的研究是首次在人体中进行的、开放标签、单剂量、剂量递增的1期试验，以评估 C135-LS和C144-LS复方制剂在健康志愿者中的安全性和药代动力学。

Project Summary The Coronavirus Disease 2019 (COVID-19) pandemic is currently gripping the world without a known cure or prevention. Aside from the health consequences, the necessary decrease in human activity has resulted in economic losses without modern precedent, especially in the developing world where health care and sanitation were not sufficient even prior to the pandemic. Innumerable efforts are being undertaken to develop vaccines to SARS-CoV-2 and it is likely that antibodies will be essential for protection. COVID-19 antibody therapy in the form of polyclonal plasma from convalescent individuals is currently being explored as a therapeutic option and has been granted an emergency use authorization (EUA) by the FDA. Monoclonal antibodies may prove to be particularly useful in preventing SARS-CoV-2 infection in populations who may not mount protective immune responses to vaccination (e.g. advanced age, immunocompromise) and for post-exposure prophylaxis in individuals at high risk to develop severe COVID-19. C135 and C144 are recombinant, fully human mAbs that specifically bind SARS-CoV-2 spike protein receptor binding domain (RBD) and exhibit exceptional neutralizing activity in vitro against SARS-CoV-2. Two one-amino acid mutations have been introduced to prolong half-life and allow dose sparing. The C135-LS and C144-LS combination has shown remarkable activity in both prophylaxis and therapy experiments in several relevant animal models in both prophylaxis and treatment experiments. These preclinical data support the clinical evahe from SARS-CoV-2 and accelerate viral clearance and disease resolution in SARS-CoV-2-infected individuals. The proposed study is a first-in-human, open label, single dose, dose-escalation phase 1 trial to evaluate the safety and pharmacokinetics of the C135-LS and C144-LS combination in healthy volunteers.