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.

项目摘要 /摘要 谁需要新的，高度敏感和超特定的横向流程分析（LFA）来支持其消除的努力 Onchocerciasis，一种疾病，也称为河流失明，影响了1800万人，另有2.18亿居住 有患这种疾病的风险。大规模药物管理局（MDA）进行了尾cer症。谁批判性 需要新的诊断测试来支持启动和停止MDA程序的决策，并于2021年发布 相应的目标产品剖面（TPP）。最严格的TPP标准是测试必须是 特异性（≥99.8％）。 我们的非营利性姊妹公司药物和热带疾病的诊断（DDTD）于2020年和2021年被 全球卫生工作队（TFGH）和美国国际发展机构（USAID）开发 新的杂尾诊断的新快速诊断测试。我们成功地制定了由两个小说O组成的评估。 在测定条上排列为两种不同的测试线的伏尔图鲁斯抗原。在独立评估中 疾病预防控制中心发现该测试敏感为89.6％（95％CI：79.2-95.2％，n = 58）和100％特异性（95％CI：99.95-100％， n = 194）。这意味着我们的BIPLEX测试符合TPP的敏感性和特异性要求，并且 值得注意的是，即使在下限95％CI处，其特异性也> 99.8％。鉴于这些数据，美国国际开发署已经 投入资金来评估大约10,000个人的现场评估，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动力 对于主要参与者（USAID，CDC，TFGH），我们现在要求从NIH直接到阶段II的资金 将测定法进行制造和商业化。第二阶段资金将用于（1）优化 BIPLEX测试以卷卷到卷制制造友好模式，并确保对关键试剂的访问，（2）建立 强大的制造过程，重点是最小化成本和最大化速度，SOP和QC 为制造环境验证的协议，以及我们QMS中记录的大量重复可重复性数据的数据， （3）生产100000台设备（在5个20千万次中）将捐赠给利益相关者（TFGH/USAID） 支持进一步的现场测试和跳跃启动测试。值得注意的是，利益相关者已经 赞助了我们的初始（“第一阶段”）研究，因此将对确保最大回报的既得利益 通过支持所有下游活动的投资，为我们的测试提供商业化的清晰途径。 我们恭敬地认为，我们的新测试将支持消除河流的一流工具 失明是一种有2100万活跃病例和2.18亿处高危人的疾病，将满足未满足的需求 对全球公共卫生的重要意义。