Planning for a Phase 2/2b Microbicide Study: VivaGel for HSV Prevention in Women

描述（由申请人提供）：生殖器单纯疱疹病毒（HSV）感染是一个主要的全球公共卫生问题，妇女受到感染的风险不成比例。1999-2004年，美国14-49岁人群中2型HSV （HSV-2）感染率为17.0%，其中男性为11.2%，女性为22.8%。2型单纯疱疹病毒的全球负担是惊人的。2003年，据估计全世界有5.36亿15-49岁的人感染2型单纯疱疹病毒。新感染人数为2 360万，估计流行率在发展中区域大多较高。2型单纯疱疹病毒感染者感染艾滋病毒的风险是2型单纯疱疹病毒感染者的三倍，同时感染2型单纯疱疹病毒的妇女感染艾滋病毒母婴传播的风险更高。抗病毒药物治疗对急性发作有效，每日使用可预防复发。然而，抗病毒药物不能根除潜伏感染，因此不能治愈单纯疱疹病毒感染。目前预防生殖器疱疹感染的方法有限，现有的抗病毒治疗减少但不能消除向易感伴侣传播的风险。因此，迫切需要有效的生物医学策略来预防生殖器疱疹的获得；尤其是对女性来说，因为她们面临的风险更大。局部杀微生物剂是用于阴道的产品，以保护妇女免受性传播感染（sti）。配制的SPL7013 （SPL7013凝胶，或VivaGel）是一种新型候选杀微生物剂，在临床前研究和一系列I期试验中被证明是安全且耐受性良好的。VivaGel是目前唯一被提议用于预防生殖器HSV-2感染的候选杀微生物剂。这项拟议的R34计划拨款将允许全面设计一项2/2b期试验，以确定阴道应用SPL7013凝胶预防女性HSV-2感染的有效性、安全性、耐受性和可接受性。由于旨在评估杀微生物剂和疫苗功效的试验之间有许多相似之处，我们建议以从艾滋病毒杀微生物剂试验和HSV疫苗试验（包括NIAID赞助的HERPEVAC研究）中获得的经验为基础。VivaGel疱疹预防团队由哥伦比亚大学、家庭健康国际和Starpharma的资深研究人员组成。该团队在合作方面有着良好的记录，在2型单纯疱疹病毒和性传播感染的治疗和预防以及建立和开展临床试验方面拥有丰富的专业知识。因此，我们有能力管理临床研究的所有研究材料的规划和开发，该研究被称为“2/2b期双盲、随机、安慰剂对照研究，研究3% SPL7013凝胶（VivaGel）预防女性生殖器疱疹感染的安全性和有效性”。以下是计划过程中将要调查的关键领域的例子：治疗持续时间、研究人群、临床地点、研究评估、样本量、数据管理和统计分析、监测和报告。

DESCRIPTION (provided by applicant): Genital herpes simplex virus (HSV) infections are a major global public health problem and women are disproportionately at risk of becoming infected. The prevalence of HSV type 2 (HSV-2) infections in the United States from 1999-2004 for persons aged 14-49 years was 17.0% with 11.2% of men infected and 22.8% of women. The global burden of HSV-2 is staggering. In 2003, it was estimated that 536 million people aged 15-49 years were living with HSV-2 infection worldwide. The number of newly infected people was 23.6 million, with the estimated prevalence being mostly higher in developing regions. The risk of HIV acquisition is three times greater in HSV-2 infected persons and the risk of HIV mother-to-infant transmission is higher in women co-infected with HSV-2. Antiviral drug therapy is effective in treating acute episodes and when used daily can prevent recurrences. However, antiviral drugs do not eradicate the latent infection and hence cannot cure HSV infections. Current methods for preventing genital herpes acquisition are limited and existing antiviral therapies reduce but do not eliminate the risk of transmission to a susceptible partner. Thus, effective biomedical strategies to prevent genital herpes acquisition are urgently needed; particularly for women since they are disproportionately at risk. Topical microbicides are products intended for vaginal use to protect women against sexually transmitted infections (STIs). Formulated SPL7013 (SPL7013 Gel, or VivaGel) is a novel candidate microbicide that has been shown to be safe and well tolerated in preclinical studies and a series of phase I trials. VivaGel is currently the only candidate microbicide being proposed for the prevention of genital HSV-2 infection. This proposed R34 planning grant will permit the comprehensive design of a Phase 2/2b trial to determine the effectiveness, safety, tolerability, and acceptability of vaginally applied SPL7013 Gel in preventing HSV-2 infection in women. As there are many parallels between trials designed to assess the efficacy of microbicides and vaccines we propose to build on the experience gained from HIV microbicide trials and from HSV vaccine trials including the NIAID sponsored HERPEVAC study. We have formed a collaboration of experienced researchers from Columbia University, Family Health International, and Starpharma to create the VivaGel Herpes Prevention Team. This team has a track record of working collaboratively, has significant expertise in the fields of HSV-2 and STI treatment and prevention, and the set-up and conduct of clinical trials. Thus, we are well positioned to manage the planning and development of all study materials for the clinical study known as "A Phase 2/2b Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety and Efficacy of 3% SPL7013 Gel (VivaGel) in the Prevention of Genital Herpes Infection in Women". The following are examples of key areas that will be investigated during the planning process: duration of treatment, study population, clinical sites, study assessments, sample size, data management and statistical analysis, monitoring, and reporting. PUBLIC HEALTH RELEVANCE (provided by applicant): Genital herpes simplex virus (HSV) infections are a major global public health problem and women are disproportionately at risk of becoming infected. Formulated SPL7013 (SPL7013 Gel, or VivaGel) is currently the only candidate microbicide being proposed for the prevention of genital HSV-2 infection. This proposed R34 planning grant will permit the comprehensive design of a Phase 2/2b trial to determine the effectiveness, safety, tolerability, and acceptability of vaginally applied SPL7013 Gel in preventing HSV-2 infection in women.