CAP:Evaluation of a Dengue Vaccine in Adults with Preexisting Flavivirus Immunity

CAP：对已有黄病毒免疫力的成人进行登革热疫苗评估

• 批准号: 10272192
• 负责人: Stephen Whitehead
• 金额: $ 9.62万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10272192
• 关键词: 12 year old; 17 year old; 4 year old; Acceleration; Admixture; Adolescent; Adult; Age; Agreement; Antibodies; Area; Attenuated; Attenuated Vaccines; Biological Assay; Child; Clinical; Clinical Research; Clinical Trials; Controlled Clinical Trials; Databases; Dengue; Dengue Vaccine; Dose; Double-Blind Method; Enrollment; Evaluation; Flavivirus; Funding; Genetic; Goals; Human; Immune response; Immunity; Individual; Infant; Medical Research; National Institute of Allergy and Infectious Disease; Phase; Placebos; Program Evaluation; Safety; Sampling; Sampling Studies; Serological; Thailand; Vaccination; Vaccines; Viremia; Virus; Work; age group; base; cohort; coronavirus disease; experience; follow-up; immunogenicity; programs; vaccine candidate

A detailed statement of work was prepared to describe the activities to be carried out by the AFRIMS group in Bangkok, Thailand. An Interagency Agreement (A-AI-12-051-0000-0000) was executed between NIAID and the U.S. Army Medical Research and Materiel Command and became effective on 09-01-2012. This agreement governs the activities between NIAID and AFRIMS and was initially funded by the NIAID Concept Acceleration Program (CAP) and the Division of Clinical research. CAP funding will be used to support this clinical trial, including the required serological assays, viremia assays, and other clinical activities associated with the evaluation of the tetravalent dengue vaccine. The purpose of this project is to evaluate a live attenuated tetravalent DENV vaccine candidate with regard to safety, tolerability, genetic stability, and immunogenicity in humans, and to study the host's immune response to these viruses. Vaccination will occur in an age de-escalation manner, beginning with adults, followed by adolescents, older children, and finally younger children. Six months after primary vaccination, adult subjects will receive a second dose of tetravalent vaccine and will be followed for an additional 6 months. Two different vaccine admixtures, TV003 and TV005 will be studied in adults. Other age cohorts will only receive TV005. The study will enroll 294 subjects in a double-blind, placebo-controlled clinical trial. Adult cohort received dose 1 on Dec 6, 2014 and dose 2 on June 6, 2015. Adolescent cohort (13 - 17 years old) dosed Mar 2015 (3-YR follow-up ended Mar 2018) Older child cohort (5 - 12 years old) dosed Aug 2015 (3-YR follow-up ended Aug 2018) Younger child cohort (1 - 4 years old) dosed Nov 2015 (3-YR follow-up ended Nov 2018) Currently, all subjects have completed the follow-up phase of the study. The follow-up period was initially set for 1 year, but the US FDA has asked that we follow-up individuals for a period of 3 years (based on the Sanofi-Pasteur Dengvaxia experience). This extended follow-up period also delayed the planned unblinding of the study. Since the last vaccinees was enrolled in the study on Nov 7, 2015, the 3-year follow-up period ended in November 2018. During 2019, the safety databases were locked and the study has been unblinded. All remaining study samples were transferred to the US (LVD and WRAIR) in Apr 2019. Final antibody assays for the year 3 samples can now be completed (delayed due to COVID).

准备了一份详细的工作声明，以描述泰国曼谷的Afrims Group将要进行的活动。 NIAID和美国陆军医学研究和物资司令部之间执行了一项机构间协议（A-AI-12-051-0000-0000），并于2012年9月1日生效。该协议控制着NIAID和AFRIMS之间的活动，最初由NIAID概念加速计划（CAP）和临床研究部资助。 CAP资金将用于支持这项临床试验，包括与四龙龙鸡疫苗评估相关的所需血清学分析，病毒血症测定和其他临床活动。 该项目的目的是评估人类的安全性，耐受性，遗传稳定性和免疫原性，并研究宿主对这些病毒的免疫反应。疫苗接种将以年龄降低的方式发生，从成年人开始，然后是青少年，大儿童和最终年幼的孩子。初次疫苗接种后六个月，成年受试者将接受第二剂四剂量疫苗，并将再接受6个月的次数。成人将研究两种不同的疫苗混合物，TV003和TV005。其他年龄段只能接收TV005。该研究将在一项双盲，安慰剂对照的临床试验中招募294名受试者。 成人队列于2014年12月6日接受剂量1，并于2015年6月6日接受剂量2。 青少年队列（13-17岁）2015年3月（3年后随访2018年3月） 年龄较大的儿童队列（5-12岁）2015年8月的服用（2018年8月3日随访） 年轻的儿童队列（1-4岁）于2015年11月服用（3年后随访于2018年11月结束） 目前，所有受试者都完成了研究的后续阶段。后续期最初设定了1年，但美国FDA要求我们跟进个人3年（基于Sanofi-Pasteur Dengvaxia的经验）。 这个延长的随访期也延迟了计划的研究。 自从2015年11月7日进行了最后一次疫苗以来，这项研究截至2018年11月。2019年期间，安全数据库被锁定，该研究没有盲目。 所有其余的研究样本均在2019年4月转移到美国（LVD和WRAIR）。现在可以完成3年级样本的最终抗体测定（由于共同导致）。