Cervical Cancer Prevention Prebiotic Device

预防宫颈癌益生元装置

• 批准号: 10252708
• 负责人: Joanna Elizabeth Ellington
• 金额: $ 40万
• 依托单位: GLYCIOME, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-17 至 2023-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252708
• 关键词: Acidity; Advanced Development; American; Bacteria; Biology; Biometry; Buffers; Businesses; Cancer Patient; Caring; Cell Proliferation; Cells; Cervicitis; Cessation of life; Clinical Trials; Data; Devices; Diagnosis; Direct Costs; Disease; Dose; Ecology; Enrollment; Epithelial; Ethnic Origin; Evaluation; Event; Excipients; Gel; Genitourinary system; Growth; Guidelines; HPV-High Risk; Health; Healthcare; High Prevalence; High-Risk Cancer; Hospitals; Human; Human Papillomavirus; Human papilloma virus infection; Incidence; Inflammation; Insurance; Lactobacillus; Legal patent; Link; Lubricants; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Manufacturer Name; Marketing; Measures; Medicaid; Medical Device; Mucous Membrane; Oncogenic; Osmolalities; Pathway interactions; Perception; Phase; Physiological; Poverty; Prevention; Process; Property; Public Health; Publishing; Puerto Rican; Puerto Rico; Race; Records; Reporting; Resistance; Resources; Risk Factors; Rural; Safety; Sales; Self-Direction; Shipping; Small Business Technology Transfer Research; Time; Tissue Model; Underserved Population; Vagina; Vaginal Douching; Water; Woman; base; biomaterial compatibility; black women; cancer care; cancer cell; cancer prevention; cancer risk; cell injury; cervical cancer prevention; cervicovaginal; commercialization; cost; cytokine; design; dysbiosis; efficacy trial; flexibility; health care availability; immunotoxicity; improved functioning; in vitro Model; innovation; manufacturing scale-up; medical schools; microbial; microbiota; mortality; mortality risk; multidisciplinary; novel; pathobiont; pathogen; pre-clinical; prebiotics; preclinical safety; prevent; product development; prototype; reproductive tract; tumorigenesis; vaginal microbiome; vaginal microbiota; vaginal mucosa; wasting

A novel, intravaginal prebiotic-gel (“PreBioGyn”) is proposed for cervical cancer prevention, through optimization of vaginal health and treatment of vaginal dysbiosis (pathogen and pathobiont overgrowth ), related to high-risk human papillomavirus (hrHPV) persistence and oncogenesis. PreBioGyn is an OTC user-directed, Class 2 medical device, uniquely innovative for women in Low Resource Settings (LRS), at greatest risk of death from cervical cancer. Increased rates of hrHPV persistence and cervical cancer are directly and indirectly linked to vaginal dysbiosis, due to elevations in vaginal pH levels, depletion of beneficial vaginal microbiota (e.g. Lactobacillus crispatus), and disruption of the mucosal barrier. Cervicitis and reduced vaginal acidity are leading risk factors for cervical cancer formation and progression. There is a significant need for an affordable, easy-to use vaginal product that optimizes vaginal pH, microbiota and mucosal function, to prevent cervical cancer . Existing vaginal pH “correcting” buffer-gels lower pH, but harm Lactobacillus and mucosal cells and/or don’t conform to WHO guidelines for vaginal safety. This is of critical public health significance given that ~90% of women report use of at least one vaginal product in any past 90 days, with use of such products increasing urogenital events (e.g. vaginal dysbiosis) 3-fold. In fact, a significant overlap occurs between women with high vaginal product use, hrHPV persistence and cervical cancer incidence, due, in part, to product-related vaginal microbiome and mucosa damage. Preliminary data show that the PreBioGyn patent-pending gel, with a novel prebiotic ingredient combination, supports L. crispatus while suppressing cervical cancer-linked P. bivia growth and is unparalleled in mucosal safety. Glyciome and academic partners (Brigham &Women’s Hospital and Univ of Puerto Rico School of Medicine) propose Phase 1 STTR studies to establish preclinical safety, efficacy and feasibility of the prebiotic gel and novel applicator (low-waste and shipping cost, enhanced user-ease and comfort). Successful completion of Phase 1 will demonstrate the following. 1) Vaginal biocompatibility of the gel in a physiologically relevant human in-vitro model vs leading buffer-gels, based on quantitative measures of: no cervicovaginal cell damage, inflammation and/or immunotoxicity; selective epithelial colonization by Lactobacilli; and no enhanced proliferation of pathobionts or cervical cancer cells. 2) User perception and acceptability of gel and applicator vs leading gels in quantifiable milestones of acceptance. 3) Physicochemical and functional properties of the gel over time and vs leading gels to demonstrate stability, and superior functionality and conformance with recommended guidelines. 4) Final design of an Integrated Manufacturing Prototype for coordination with the proposed manufacturer. Successful completion of the project will lead to STTR Phase 2 manufacturing scale up, clinical trials for optimization of vaginal health and prevention of cervical cancer, and filing for FDA device clearance with de novo vaginal health claims. Glyciome has assembled an expert team in: product development; manufacturing/sales; biostatistics; genital tract biology; and global cervical cancer care.

通过优化，提出了一种用于预防宫颈癌的新型阴道内prebiotic-gel（"PreBioGyn"）。 阴道健康和治疗阴道生态失调（病原体和致病菌过度生长 ），与高风险有关 人乳头瘤病毒（hrHPV）持久性和肿瘤发生。PreBioGyn是 OTC用户导向，2类 医疗器械，为低资源环境（LRS）中的女性提供的独特创新， 宫颈癌hrHPV持续性和宫颈癌发生率的增加与以下因素直接和间接相关： 阴道微生态失调，由于阴道pH水平的升高，有益的阴道微生物群的消耗（例如， 卷曲乳杆菌）和破坏粘膜屏障。宫颈炎和阴道酸度降低是导致 子宫颈癌的形成和发展的危险因素。有一个负担得起的，容易的显着需求， 使用优化阴道pH值的阴道产品， 微生物群和粘膜功能，以预防宫颈癌 . 现有的阴道pH值"校正"缓冲凝胶降低pH值，但伤害乳酸菌 和/或不 符合WHO阴道安全指南。这对公共卫生至关重要 鉴于约90%的 女性报告在过去90天内使用至少一种阴道产品， 泌尿生殖系统事件（如阴道生态失调）3倍。事实上，高血压妇女与低血压妇女之间存在显著的重叠。 阴道产品使用、hrHPV持续性和宫颈癌发病率，部分原因是产品相关的阴道 微生物组和粘膜损伤。初步数据显示，PreBioGyn正在申请专利的凝胶，具有新颖的 益生元成分组合，支持L.卷曲，同时抑制宫颈癌相关的P.bivia生长 并且在粘膜安全性方面无与伦比。Glyciome和学术合作伙伴（布里格姆妇女医院和大学 （波多黎各医学院）提出1期STTR研究，以确定临床前安全性、有效性和 益生元凝胶和新型施用器的可行性（低浪费和运输成本，增强的用户易用性， comfort）。第一阶段的成功完成将证明以下几点。1)凝胶的阴道生物相容性 在生理学相关的人体外模型中与领先的缓冲凝胶相比，基于以下定量测量： 宫颈阴道细胞损伤、炎症和/或免疫毒性;乳酸杆菌选择性上皮定植; 并且没有增强致病菌或宫颈癌细胞的增殖。2)凝胶的用户感知和可接受性 以及施用器与领先凝胶在可量化的验收里程碑中的对比。3)理化和功能 凝胶随时间的性质和与领先的凝胶相比，证明了稳定性和上级功能性， 符合推荐的指南。4)集成制造原型的最终设计 与建议的制造商进行协调。该项目的成功完成将导致STTR第2阶段 扩大生产规模，优化阴道健康和预防宫颈癌的临床试验，以及 申请FDA的设备许可，并重新提出阴道健康声明。Glyciome在以下方面组建了一个专家团队： 产品开发;制造/销售;生物统计学;生殖道生物学;以及全球宫颈癌护理。