CoVPN 3502 / ACTIV-2/A5401

CoVPN 3502 / ACTIV-2/A5401

• 批准号: 10318831
• 负责人: Judith S. Currier
• 金额: $ 1980.75万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-24 至 2022-08-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318831
• 关键词: AIDS clinical trial group; AIDS/HIV problem; Address; Affect; Aging; Anti-Retroviral Agents; Antiviral Agents; Area; Behavioral; Biological Markers; Blood; California; Cardiovascular system; Clinical; Clinical Research; Clinical Trials; Collaborations; Communication; Conduct Clinical Trials; Development; Disease; Disease remission; Drug resistance in tuberculosis; Epidemic; Evaluation; Funding; Goals; HIV; HIV Infections; HIV/TB; Health; Hepatitis B; Hepatitis B Virus; Immune; Immunologics; Industry Collaboration; Infection; Infrastructure; International; Intervention; Knowledge; Laboratories; Leadership; Los Angeles; Maintenance; Mental Health; Metabolic; Morbidity - disease rate; Multidrug-Resistant Tuberculosis; Neurologic; Obesity; Occupational activity of managing finances; Phase; Population; Prevention; Prevention and Treatment of Opportunistic Infection; Protocols documentation; Publishing; Regimen; Research; Research Personnel; Resources; Risk; Science; Specimen; Structure; System; Testing; Therapeutic; Therapeutic Intervention; Tissues; Training; Tuberculosis; Universities; Virus Diseases; active method; acute infection; antiretroviral therapy; burden of illness; chronic infection; collaboratory; community engagement; community involvement; comorbidity; comparative efficacy; data management; design; drug-sensitive; efficacy trial; improved; innovation; mortality; multidisciplinary; neutralizing antibody; novel; operation; prevent; protocol development; social; statistics; therapeutic vaccine; treatment guidelines; virology

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.

抽象的 第三阶段，随机，双盲，安慰剂对照研究，评估 抗尖峰SARS-COV-2单克隆抗体的功效和安全性在防止感染SARS-COV-2的个体的家庭接触中SARS-COV-2感染（COVPN 3502） SARS-COV-2的传播主要通过人与人的接触和呼吸发生 液滴传输（LAI，2020）。感染SARS-COV-2的人的家庭接触是 收购感染的高风险，传输速率范围从大约10％到 15％。从家庭接触中获取感染感染的大多数人会发展 COVID-19的症状（Burke，2020）（Jing，2020），（BI，2020）（Li，2020b）。预防急切 需要降低传播率和/或减少症状疾病的发生。 理想情况下，已知暴露后需要尽快给予预防 源源性感染之间的持续时间与新感染个体的症状发展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（NP）样品中的SARS-COV-2 RT-PCR在感染后几天内变得阳性（Rockx，2020）。预防的理想药物应具有快速作用和单克隆抗体（MAB）联合疗法，并具有两种不同的单克隆抗体，它们结合了SARS-COV-2尖峰（S）蛋白质的不同区域，这些抗体与结合并促进进入宿主细胞的部分，以实现这些目标。 针对SARS-COV-2的MAB组合可预防暴露后预防，可以防止疾病发展或减少病毒性获取或脱落，这对于减少病毒的传播以及限制症状和感染后不良后果可能是关键。 考虑到这次暴发的速度以及几乎所有的影响 在全球范围内，社区迫切需要开发安全有效的干预措施，以减缓SARS-COV-2病毒的传播并减少与之相关的不良后果 有症状的疾病。 这项研究旨在评估共同管理Regn10933+Regn10987组合疗法（“ Regn10933+Regn10987”）的效率和安全性，以减少 SARS-COV-2感染的比例并防止Covid-19疾病的发展 （有症状的SARS-COV2感染），家庭接触SARS-COV-2的个体后 感染。 Activ-2/A5401：COVID-19（适应COVID）的门诊病人的自适应平台治疗试验 - BRII Biosciences Agent Adapt Out Covid是一项总体方案，旨在评估研究剂治疗Covid-19的症状非医院成年人的安全性和有效性。它始于II期评估，然后过渡到有前途的药物的更大阶段III评估。这种补充代表了BRII生物科学剂的活性。 该试验是一个随机，失明，受控的自适应平台，可以在研究过程中添加和删除代理，以有效测试新代理在同一试验基础设施中针对安慰剂。当同时测试两个或多个新代理时，如果可行，将使用同一安慰剂。 II期评估中的主要结果度量将是症状的持续时间，类似于门诊影响研究的结果，鼻咽（NP）拭子对SARS-COV-2 RNA的检测丢失以及安全性。在最后一次参与到该代理或安慰剂组的最后一次参与后，将在第三阶段继续评估II期代理的确定是否会继续进行评估。如果继续，则从第三阶段的参与者中收集的数据将包括在第三阶段评估中。 III期评估是符合研究定义标准的代理商的II期试验的延续，并为此提供了足够的研究代理。代理商还可以基于试验监督委员会（TOC）评估直接进入第三阶段评估。全力以赴的III期试验将评估每种选定的研究剂与安慰剂相比的有效性，以防止Covid-19的非医院成年人的住院和死亡。 当信息从试验内部或外部获得，表明将进一步的随机化为安慰剂是不合适的，该协议将进行修改。