Expanded Phase II Trial of Carraguard for Prevention of HPV Infection

Carraguard 预防 HPV 感染的 II 期扩展试验

• 批准号: 8326236
• 负责人: MARK H. EINSTEIN
• 金额: $ 80.41万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2016-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326236
• 关键词: Accounting; Address; Adherence; Adoption; Age-Years; American; Animal Model; Anti-HIV Agents; Antiviral Agents; Behavioral; Biological; Biological Assay; Biological Markers; Carrageenan; Cells; Centers for Disease Control and Prevention (U.S.); Cervical; Cervical Intraepithelial Neoplasia; Characteristics; Clinical; Clinical Research; Clinical Trials; Cold Chains; Cultured Cells; DNA; Data; Defensins; Development; Double-Blind Method; Drug Formulations; Effectiveness; Enrollment; Environment; Exposure to; Female; Frequencies; Future; Gel; Generations; Genital system; Goals; HIV; Health; Hispanics; Host Defense; Human; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; In Vitro; Incidence; Infection; Infection prevention; Injection of therapeutic agent; Inorganic Sulfates; Irrigation; Knowledge; Laboratories; Laboratory Study; Lesion; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Medical center; Medicine; Modeling; Mus; New York; Oncogenic; Pap smear; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Placebos; Polysaccharides; Population; Population Heterogeneity; Premalignant; Prevention; Prevention strategy; Public Hospitals; Questionnaires; Randomized; Randomized Clinical Trials; Reporting; Research; Research Design; Research Personnel; Risk; Safety; Sampling; Screening procedure; Seaweed; Seminal Plasma; Seminal fluid; Series; Sexually Transmitted Diseases; Specimen; Staining method; Stains; Swab; Target Populations; Testing; Therapeutic; Time; University Hospitals; Unspecified or Sulfate Ion Sulfates; Vaccination; Vaccines; Vagina; Vaginal Douching; Virus Diseases; Vision; Visit; Woman; age group; antimicrobial; antimicrobial peptide; arm; base; cervical cancer prevention; chemokine; college; condoms; cost; cytokine; design; efficacy testing; efficacy trial; follow-up; high risk; hydroxyethylcellulose; microbicide; older women; phase 3 study; placebo controlled study; preclinical study; prevent; public health relevance; sexually active; success; tool; transmission process; uptake; vaginal microbicide

DESCRIPTION (provided by investigator): There are approximately 7.5 million Americans infected with a documented new human papillomavirus (HPV) every year. Rates of persistent HPV, cervical intraepithelial neoplasia, and cervical cancer are especially high in Bronx, NY. The early success of the HPV L1-based vaccines is encouraging, but when used alone, and with limited early adoption, will not eliminate HPV infections, abnormal Pap tests, or prevent all cervical cancers. Several vaginal microbicides have been tested for efficacy against HIV. However, there are no clinical trials to date that have been conducted to primarily determine efficacy against other sexually transmitted infections (STI). This project builds on in vitro and animal model studies demonstrating that carageenans provide protection against human papillomavirus (HPV) infection at concentrations that are 1000-fold less than those required to inhibit HIV. A recently completed Phase III efficacy trial testing the ability of Carraguard to prevent HIV infection in women revealed that Carraguard is safe and that the frequency of HIV infection was lower in the Carraguard arm than in the placebo group. These findings provide the framework for proposing a trial to test Carraguard efficacy against HPV. Two hundred Bronx women will be enrolled in an expanded Phase II randomized double-blind placebo controlled study to evaluate the efficacy of Carraguard gel in preventing incident HPV infections over a one year period. This trial will provide the opportunity to build on translational laboratory studies designed to enhance our knowledge of efficacy and mechanism of activity against HPV as well as mucosal safety. Female genital tract secretions will be collected by cervicovaginal lavage (CVL) at different times post-application and spiked with HPV pseudovirions in the absence and presence of seminal plasma to evaluate the antiviral activity of Carraguard ex vivo. We will also further explore the safety of Carraguard by collecting CVL and vaginal swabs following repeated application to determine if Carraguard induces changes in the genital tract mucosal environment or alters vaginal flora. This proposed project will be based at the Albert Einstein College of Medicine (AECOM) and will include its primary affiliated University Hospital, Montefiore Medical Center, and Jacobi Medical Center, a New York public hospital and long-time affiliate of AECOM. The project will also include the Population Council, a nonprofit, non-governmental research organization located in Manhattan. This partnership with Population Council reflects a common vision to aggressively pursue cutting edge STI prevention strategies that include microbicides for HPV prevention. If Carraguard proves active against HPV, this would support further development of Carraguard as a promising formulation vehicle, to which potent anti-HIV agents could also be potentially added to provide an effective combination microbicide. PUBLIC HEALTH RELEVANCE: The primary goal is to test the efficacy of a microbicide in preventing new HPV infections. Decreasing HPV rates would have a significant impact on reducing persistent HPV infection, abnormal Pap tests, and cervical cancer nationally and worldwide.

描述（由研究者提供）：每年大约有 750 万美国人感染记录在案的新型人乳头瘤病毒 (HPV)。纽约州布朗克斯区的持续性 HPV、宫颈上皮内瘤变和宫颈癌的发病率特别高。基于 HPV L1 的疫苗的早期成功令人鼓舞，但单独使用且早期采用有限，无法消除 HPV 感染、巴氏试验异常或预防所有宫颈癌。几种阴道杀微生物剂已经过针对艾滋病毒的功效测试。然而，迄今为止还没有进行临床试验来初步确定对其他性传播感染（STI）的功效。该项目建立在体外和动物模型研究的基础上，证明角叉菜胶可以在比抑制 HIV 所需浓度低 1000 倍的浓度下提供针对人乳头瘤病毒 (HPV) 感染的保护作用。最近完成的一项 III 期功效试验测试了 Carraguard 预防女性 HIV 感染的能力，结果表明 Carraguard 是安全的，并且 Carraguard 组的 HIV 感染频率低于安慰剂组。这些发现为提议进行一项试验来测试 Carraguard 对 HPV 的功效提供了框架。 200 名布朗克斯女性将参加一项扩大的 II 期随机双盲安慰剂对照研究，以评估 Carraguard 凝胶在一年内预防 HPV 感染的功效。该试验将为转化实验室研究提供机会，旨在增强我们对 HPV 功效和活性机制以及粘膜安全性的了解。在应用后的不同时间通过宫颈阴道灌洗（CVL）收集女性生殖道分泌物，并在精浆不存在和存在的情况下掺入 HPV 假病毒粒子，以评估 Carraguard 离体的抗病毒活性。我们还将通过重复使用后收集CVL和阴道拭子来进一步探讨Carraguard的安全性，以确定Carraguard是否会引起生殖道粘膜环境的变化或改变阴道菌群。该拟议项目将设在阿尔伯特·爱因斯坦医学院 (AECOM)，包括其主要附属大学医院、蒙蒂菲奥里医疗中心和雅可比医疗中心（纽约公立医院和 AECOM 的长期附属机构）。该项目还将包括人口委员会，这是一个位于曼哈顿的非营利性非政府研究组织。与人口委员会的这种伙伴关系体现了积极追求尖端性传播感染预防策略的共同愿景，其中包括用于预防 HPV 的杀菌剂。如果 Carraguard 被证明对 HPV 具有活性，这将支持 Carraguard 作为一种有前途的制剂载体的进一步开发，其中还可能添加有效的抗 HIV 药物，以提供有效的组合杀微生物剂。 公共卫生相关性：主要目标是测试杀菌剂在预防新的 HPV 感染方面的功效。降低 HPV 感染率将对减少全国和全世界的持续 HPV 感染、巴氏试验异常和宫颈癌产生重大影响。