CoVPN 3502 / ACTIV-2/A5401

摘要 一项3期随机、双盲、安慰剂对照研究 抗SARS-CoV-2单抗预防SARS-CoV-2感染者家庭接触者感染SARS-CoV-2的有效性和安全性 SARS-CoV-2主要通过人与人之间的接触和呼吸道传播 液滴传输(Lai，2020)。与感染SARS-CoV-2人士有家居接触者包括 有感染的高风险，传播率约为10%至 15%。通过家庭接触感染的大多数人都会患上 新冠肺炎的症状(伯克，2020)(景，2020)，(毕氏，2020)(李，2020b)。预防是当务之急 需要减少传播率和/或减少症状性疾病的发生。 理想情况下，预防措施需要在已知的暴露后尽快给予，因为 从源头个体出现症状感染到新感染者出现症状之间的持续时间被认为约为5天，可能的范围为2至14天(Lauer，2020)(Li，2020a)。动物模型表明，鼻咽样本中的SARS-CoV-2 RT-PCR在感染后几天内呈阳性(Rockx，2020)。理想的预防药物应该是快速有效和高效的，并且应该保护免受多种病毒变异的影响。为了实现这些目标，已经开发出一种单抗联合疗法，用两种不同的单抗结合SARS-CoV-2刺突蛋白(S)的不同区域，这两种单抗结合并促进进入宿主细胞。 针对SARS-CoV-2的单抗组合用于暴露后预防，既可以防止疾病的发展，也可以减少病毒的获取或脱落，这可能是减少病毒传播和限制感染后症状和不良后果的关键。 鉴于疫情蔓延的速度以及它对几乎所有 在全球范围内，迫切需要制定安全有效的干预措施，以减缓SARS-CoV-2病毒的传播，并减少与 症状性疾病。 本研究旨在评估联合应用REGN10933+REGN10987联合治疗(“REGN10933+REGN10987”)以减少 非典冠状病毒2型感染比例与新冠肺炎病的预防发展 (有症状的SARS-CoV2感染)，在家庭接触感染SARS-CoV-2的个人后 感染。 ACTV-2/A5401：新冠肺炎门诊患者的适应平台治疗试验(适应出柯萨奇病毒)-Brii生物科学试剂 Adapt Out COVID是一项评估研究药物治疗有症状的非住院成人新冠肺炎的安全性和有效性的主方案。它从第二阶段评估开始，然后过渡到更大的第三阶段评估，对有希望的药物进行评估。本附录代表Brii Biosciences代理的活动。 该试验是一个随机、盲目、受控的适应性平台，允许在研究过程中添加和删除药物，以便在相同的试验基础设施中有效地测试新药物与安慰剂的对比。当两种或两种以上的新药物同时进行测试时，如果可行，将使用相同的安慰剂。 在第二阶段评估中，主要的结果衡量标准将是症状持续时间，类似于门诊流感研究的结果，鼻咽拭子检测不到SARS-CoV-2RNA，以及安全性。第二阶段药物是否将继续在第三阶段接受评估的决定，将在最后一名被随机分配到该药物或安慰剂组的参与者完成他们第28天的第二阶段访问后做出。如果继续进行，从第二阶段登记的参与者那里收集的数据将被纳入第三阶段评估。 第三阶段评估是第二阶段试验的延续，适用于符合研究定义的进一步评估标准的药物，并且有足够的研究试剂可用。代理人也可以根据审判监督委员会(TOC)的评估直接进入第三阶段评估。这项完全有效的第三阶段试验将评估每一种选定的研究药物与安慰剂相比在预防未住院的新冠肺炎成人患者住院和死亡方面的有效性。 当从试验内部或外部获得的信息表明进一步随机服用安慰剂是不合适的时，该方案将被修改。

Abstract A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2 (CoVPN 3502) Transmission of SARS-CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020). Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection from household contacts develop symptoms of COVID-19 (Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b). Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic disease. Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of time between symptomatic infection in the source individual and the development of symptoms in newly infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020) (Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. Given the speed at which this outbreak has spread and how it has impacted almost every community globally, there is an urgent need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with symptomatic disease. This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure to individuals with SARS-CoV-2 infection. ACTIV-2/A5401: Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt Out COVID) – Brii Biosciences Agent Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19. It begins with a phase II evaluation, followed by a transition into a larger phase III evaluation for promising agents. This supplement represents activity for the Brii Biosciences Agent. The trial is a randomized, blinded, controlled adaptive platform that allows agents to be added and dropped during the course of the study for efficient testing of new agents against placebo within the same trial infrastructure. When two or more new agents are being tested concurrently, the same placebo will be used, if feasible. The primary outcome measures in the phase II evaluation will be duration of symptoms, similar to the outcome used for outpatient influenza studies, loss of detection of SARS-CoV-2 RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a phase II agent will continue to be evaluated in phase III will be made after the last participant randomized to that agent or placebo group completes their day 28 phase II visit. If continued, data collected from participants enrolled in phase II will be included in the phase III evaluation. The phase III evaluation is a continuation of the phase II trial for agents that meet study-defined criteria for further evaluation and for which sufficient investigational agent is available. An agent may also enter directly into phase III evaluation based on Trial Oversight Committee (TOC) assessments. The fully powered phase III trial will evaluate the efficacy of each selected investigational agent compared to placebo to prevent hospitalization and death in non-hospitalized adults with COVID-19. The protocol will be amended when information becomes available from within or outside of the trial indicating that further randomization to a placebo is inappropriate.