SUPPORTING WHO ONCHOCERCIASIS ELIMINATION PROGRAMS: PROGRESSING A HIGHLY SENSITIVE AND ULTRA-SPECIFIC RAPID DIAGNOSTIC TEST TO COMMERCIALIZATION READINESS

支持世界卫生组织根除盘尾丝虫病计划：推进高度敏感和超特异性的快速诊断测试以做好商业化准备

• 批准号: 10697164
• 负责人: Marco Antonio Biamonte
• 金额: $ 92.15万
• 依托单位: BIG EYE DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-16 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697164
• 关键词: Adopted; Adoption; Advisory Committees; Affect; Agency for International Development; Antibodies; Antigens; Binding; Biological Assay; Clinical Sensitivity; Contracts; Data; Devices; Diagnostic; Diagnostic tests; Disease; Ensure; Evaluation; Friends; Funding; Goals; Health; IgG4; Individual; Intestinal Volvulus; Investments; Manufacturer; Marketing; National Institute of Allergy and Infectious Disease; Noise; O Antigens; Ocular Onchocerciasis; Onchocerciasis; Persons; Pharmaceutical Preparations; Phase; Prevalence; Process; Protocols documentation; Public Health; Rapid diagnostics; Reagent; Recombinants; Recommendation; Reproducibility; Research; Risk; Sales; Secure; Sensitivity and Specificity; Sister; Source; Specificity; Speed; Surveys; System; Testing; Time; Tropical Disease; United States National Institutes of Health; Validation; Variant; Vendor; commercialization; commercialization readiness; cost; cost effectiveness; design; detector; diagnostic tool; field study; fighting; global health; improved; interest; large scale production; lateral flow assay; manufacture; manufacturing process; meetings; novel; novel diagnostics; pathogen; programs; public health relevance; sample collection; tool

PROJECT SUMMARY / ABSTRACT WHO needs new, highly sensitive and ultra-specific lateral flow assays (LFA) to support its endeavors to eliminate onchocerciasis, a disease also known as river blindness affecting 18 million people, with another 218 million living at risk of contracting the disease. Onchocerciasis is fought by mass drug administration (MDA). WHO critically needs new diagnostic tests to support decisions to start and stop MDA programs and released in 2021 the corresponding desired target product profiles (TPPs). The most stringent TPP criterion is that the test must be extraordinarily specific (≥ 99.8%). Our non-profit sister company Drugs & Diagnostics for Tropical Diseases (DDTD) was hired in 2020 and 2021 by the Task Force for Global Health (TFGH) and the US Agency for International Development (USAID) to develop a new rapid diagnostic test for onchocerciasis. We succeeded in developing an assay composed of two novel O. volvulus antigens that are arranged as two distinct test lines on the assay strip. In an independent evaluation, the CDC found the test to be 89.6% sensitive (95% CI: 79.2-95.2%, N=58) and 100% specific (95% CI: 99.95-100%, N=194). This means that our biplex test meets the sensitivity and specificity requirements of both TPPs and, remarkably, its specificity is >99.8% even at the lower bound 95% CI. In view of these data, USAID has already committed funding to evaluate the assay in the field on approximately 10,000 individuals, which will be conducted by the TFGH in early 2023. Given these exciting results, the massive relevance for public health, and the big momentum already garnered with key players (USAID, CDC, TFGH), we are now requesting Direct-to-Phase II funding from the NIH to swiftly progress the assay to manufacturing and commercialization. Phase II funding will be used to (1) optimize the biplex test in a reel-to-reel manufacturing-friendly mode, and to secure access to critical reagents, (2) establish a robust manufacturing process, with a focus on minimizing costs and maximizing speed, with SOPs and QC protocols validated for a manufacturing context, and data on lot-to-lot reproducibility data recorded in our QMS, and (3) produce 100’000 devices (in 5 lots of 20’000) that will be donated to the stakeholders (TFGH/USAID) to support further field testing and jump-start test adoption. It is noteworthy that said stakeholders have already sponsored our initial (“Phase I”) research, hence will have a vested interest in ensuring maximum return on their investment by facilitating all downstream activities necessary to provide a clear path to commercializing our test. We respectfully submit that a first-in-class tool, such as our new test, that will support the elimination of river blindness, a disease with 21 million active cases and 218 million at-risk individuals, will address an unmet need of paramount significance for global public health.

项目概要/摘要 世卫组织需要新的、高度灵敏和超特异性的侧向层析检测（LFA）来支持其消除病毒的努力 盘尾丝虫病，一种也称为河盲症的疾病，影响着 1800 万人，另有 2.18 亿人活着 世界卫生组织 (WHO) 正在大力防治盘尾丝虫病。 需要新的诊断测试来支持启动和停止 MDA 计划的决策，并于 2021 年发布了 相应的所需目标产品概况 (TPP) 最严格的 TPP 标准是测试必须符合要求。 非常具体（≥ 99.8%）。 我们的非营利姊妹公司热带疾病药物与诊断 (DDTD) 于 2020 年和 2021 年受雇于 全球卫生工作组 (TFGH) 和美国国际开发署 (USAID) 共同制定 我们成功开发了一种由两种新型 O 组成的检测方法。 在独立的评估、测定中，将盘旋抗原排列成条上的两条不同的测试线。 CDC 发现该测试的敏感性为 89.6%（95% CI：79.2-95.2%，N=58），特异性为 100%（95% CI：99.95-100%， N=194)，这意味着我们的双工测试满足 TPP 的敏感性和特异性要求， 值得注意的是，即使在 95% CI 的下限下，其特异性也 >99.8%。 承诺资助约 10,000 人现场评估该检测，这将是 由 TFGH 于 2023 年初进行。 鉴于这些令人兴奋的结果、与公共卫生的巨大相关性以及已经获得的巨大势头 与主要参与者（美国国际开发署、疾病预防控制中心、TFGH）合作，我们现在请求 NIH 提供直接第二阶段资金，以迅速 将试验进展到制造和商业化，第二阶段资金将用于 (1) 优化 以卷对卷制造友好模式进行双相测试，并确保获得关键试剂，(2) 建立 稳健的制造流程，重点是最大限度地降低成本和最大限度地提高速度，并采用 SOP 和 QC 针对制造环境进行验证的协议，以及我们的 QMS 中记录的批次间再现性数据的数据， (3) 生产 100,000 台设备（分 5 批，每批 20,000 台），这些设备将捐赠给利益相关者（TFGH/USAID） 支持进一步的现场测试和快速启动测试的采用。 赞助了我们的初始（“第一阶段”）研究，因此将在确保其最大回报方面拥有既得利益 通过促进所有必要的下游活动来进行投资，为我们的测试商业化提供明确的途径。 我们恭敬地提出，一流的工具，例如我们的新测试，将支持消除河流 失明是一种有 2100 万活跃病例和 2.18 亿高危人群的疾病，将解决未得到满足的需求 对全球公共卫生具有重要意义。