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

规划 2/2b 期杀菌剂研究：VivaGel 用于预防女性 HSV

• 批准号: 7963312
• 负责人: Lawrence Stanberry
• 金额: $ 20.62万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7963312
• 关键词: Acute; Adverse event; Antiviral Agents; Antiviral Therapy; Archives; Area; Budgets; Case Report Form; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Clinical Trials Design; Clinical trial protocol document; Code; Collaborations; Communication; Conduct Clinical Trials; Data; Data Collection; Databases; Development; Development Plans; Double-Blind Method; Effectiveness; Elements; Ensure; Family health status; Gel; Goals; Grant; HIV; Herpes Simplex Virus Vaccines; Human Herpesvirus 2; Infant; Infection; International; Laboratories; Life; Local Microbicides; Manuals; Medical; Methods; Monitor; Mothers; National Institute of Allergy and Infectious Disease; Outcome; Outcome Study; Pamphlets; Participant; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase I Clinical Trials; Placebo Control; Population Analysis; Population Study; Positioning Attribute; Prevalence; Prevention; Principal Investigator; Procedures; Process; Protocols documentation; Public Health; Randomized; Recurrence; Regulation; Reporting; Research Design; Research Personnel; Risk; SPL7013; Safety; Sample Size; Series; Serious Adverse Event; Sexually Transmitted Diseases; Simplexvirus; Staging; Subgroup; Time; TimeLine; United States; Universities; Update; Vaccines; Vagina; Virus Diseases; VivaGel; Woman; Work; aged; base; clinical research site; data management; design; diaries; experience; genital herpes; human subject protection; latent infection; men; microbicide; novel; pre-clinical; preclinical study; prevent; programs; protocol development; public health relevance; randomized placebo controlled trial; tool; transmission process; treatment duration

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.

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，女性受感染的风险不成比例。1999-2004年，美国14-49岁人群中HSV 2型（HSV-2）感染的患病率为17.0%，其中男性感染率为11.2%，女性感染率为22.8%。HSV-2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HSV-2。新感染人数为2 360万人，估计流行率大多在发展中区域较高。HSV-2感染者感染艾滋病毒的风险高三倍，同时感染HSV-2的妇女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HSV感染。目前用于预防生殖器疱疹获得的方法是有限的，现有的抗病毒疗法减少但不能消除传播给易感伴侣的风险。因此，迫切需要有效的生物医学战略，以防止生殖器疱疹的获得，特别是对妇女来说，因为她们的风险不成比例。局部杀微生物剂是用于阴道的产品，旨在保护妇女免受性传播感染（STI）。SPL 7013凝胶（SPL 7013 Gel，或VivaGel）是一种新型的候选杀微生物剂，在临床前研究和一系列I期试验中已被证明是安全和耐受性良好的。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2/2b期试验的全面设计，以确定阴道应用SPL 7013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有效性的试验之间存在许多相似之处，我们建议以从HIV杀微生物剂试验和HSV疫苗试验（包括NIAID申办的HERPEVAC研究）中获得的经验为基础。我们与来自哥伦比亚大学、国际家庭健康组织和Starpharma的经验丰富的研究人员合作，创建了VivaGel疱疹预防团队。该团队有着良好的合作记录，在HSV-2和STI治疗和预防以及临床试验的建立和实施方面具有重要的专业知识。因此，我们有能力管理被称为“一项研究3% SPL 7013凝胶（VivaGel）预防女性生殖器疱疹感染的安全性和有效性的II/2b期双盲、随机、安慰剂对照研究”的临床研究的所有研究材料的规划和开发。以下是计划过程中将研究的关键领域示例：治疗持续时间、研究人群、临床研究中心、研究评估、样本量、数据管理和统计分析、监查和报告。 公共卫生相关性（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，女性受感染的风险过高。SPL 7013凝胶（SPL 7013 Gel，或VivaGel）是目前唯一一种用于预防生殖器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2/2b期试验的全面设计，以确定阴道应用SPL 7013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。