Evaluation of clinical outcome assessment (COA) and potential biomarkers to Facilitate Interventionaltrial for Mucopolysaccharidosis IIID Patients

临床结果评估 (COA) 和潜在生物标志物的评估，以促进粘多糖贮积症 IIID 患者的介入试验

• 批准号: 10325321
• 负责人: Srikanth Singamsetty
• 金额: $ 37.03万
• 依托单位: PHOENIX NEST, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325321
• 关键词: Affect; Authorization documentation; Awareness; Behavior; Behavioral; Biochemical; Biochemical Markers; Brain; CLN2 gene; Case Study; Cessation of life; Childhood; Clinic; Clinical; Clinical Data; Clinical Protocols; Clinical Research; Clinical Services; Clinical Trials; Clinical Trials Design; Clinical trial protocol document; Cognitive; Communities; Consultations; Contract Services; Data; Data Collection; Dementia; Development; Development Plans; Diagnosis; Disease; Disease Progression; Drug Evaluation; Electrophysiology (science); Emotional; Enrollment; Enzymes; Evaluation; Evaluation Research; Foundations; Genotype; Goals; Grant; Human; Image; Impaired cognition; Individual; Infusion procedures; International; Intervention; Intervention Studies; Intervention Trial; Investigational Therapies; Legal patent; Letters; Literature; Measurable; Measurement; Measures; Medical History; Molecular; Molecular Diagnosis; Monitor; Morals; Motor Skills; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Natural History; Nerve Degeneration; Neurocognitive; Neurologic; Neurologic Symptoms; Neuropsychology; Outcome; Outcome Measure; Pathologic; Pathology; Patient Outcomes Assessments; Patients; Phase; Phenotype; Preparation; Principal Investigator; Problem behavior; Program Development; Protocols documentation; Publications; Quality of life; Rare Diseases; Recombinants; Recommendation; Records; Research; Research Design; Research Personnel; Scientist; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Spielmeyer-Vogt Disease; Sulfatases; Surrogate Markers; Surveys; Technology; Time; TimeLine; Treatment Efficacy; Validation; Variant; Visit; Work; analytical tool; arm; biomarker development; clinical outcome assessment; clinical outcome measures; clinical predictors; clinically relevant; cohort; commercialization; compare effectiveness; control trial; design; disease registry; drug development; enzyme replacement therapy; expectation; experience; innovation; meetings; mobile application; molecular marker; outreach; participant enrollment; patient population; phase I trial; potential biomarker; primary endpoint; product development; programs; prospective; randomized placebo controlled study; research clinical testing; service providers; standard of care; success; symposium; symptomatology; tool; treatment planning; treatment response

Project Summary Sanfilippo disease (mucopolysaccharidosis type III; MPS III) is a devastating neurodegenerative lysosomal storage disorder of childhood whose pathologic features are neurologic: slowing of development, severe behavioral problems, progressive cognitive decline, dementia, and decline in motor skills leading to immobility, unresponsiveness, and death. We have focused on MPS IIID caused by a deficiency of alpha-N- acetylglucosamine-6-sulfatase (GNS). Because MPS IIID is rare (1 in a million) and affects the brain (which is difficult to treat) no cure or treatment is available and there are at least five patients in the USA to our knowledge. Sanfilippo patient organizations have 19 additional cases registered around the world (see letter of support). Dr. Patricia Dickson and Dr. Tsui-Fen Chou (LABioMed) have developed an enzyme replacement treatment (ERT) for MPS IIID. Our strategy proposes to deliver recombinant human alpha-N-acetylglucosamine-6-sulfatase (rhGNS) via intracerebroventricular infusion to effectively treat the underlying causes of the neurologic symptoms that dominate MPS III pathology. ERTs can have a dramatic effect on the quality of life and patient development especially when administered early in developments. There are several examples of successfully commercialized ERT’s (e.g. laronidase (MPS I), idursulfase (MPS II), etc.) and BioMarin recently received approval for an ERT for a form of Batten disease, CLN2. Other ERTs for MPS I, II, and IIIB are in Phase I trials. Both the FDA and investors are familiar with ERT and its commercialization path, which will greatly increase the chances of reaching a clinical trial. LABioMed has filed a US patent on rhGNS and Phoenix Nest, Inc. has licensed it. Our pivotal nonclinical and manufacturing plans are on track. We had a positive interaction with the FDA and got guidance for moving our program into the clinics. In preparation for the interventional study the recommendation was for a thorough natural history study (NHS) in the available patient population with a broad net to capture endpoints that are most likely to predict the clinical benefits in each individual. Since the number of diagnosed patients is small the collected data form each individual would be their own control at the time of intervention, where the patient will receive the recombinant enzyme. Most of the work will be executed by contracted service providers. The clinical trial itself will be conducted at NYU under the guidance of Dr. Lau. She has experience with over 10 clinical trials interventional and observational. The clinical protocol was designed by the team at Phoenix Nest with help of KOLs and clinical experts in the MPS III field. We have engaged expert third party clinical service providers to help with the execution, monitoring and data collection. Crucial data collected from the patients on this study will help us develop clinical outcomes that will be tools for measuring the efficacy of our rhGNS therapy and will be primary endpoints on the pivotal study. The success on this trial will put a step closer to executing the pivotal trial to assess the efficacy of our experimental therapy and its commercialization.

项目概要 Sanfilippo 病（粘多糖贮积症 III 型；MPS III）是一种破坏性神经退行性溶酶体疾病 儿童期储存障碍，其病理特征为神经系统：发育缓慢，严重 行为问题、进行性认知能力下降、痴呆和运动技能下降导致行动不便， 我们重点关注由 α-N- 缺乏引起的 MPS IIID。 因为 MPS IIID 很罕见（百万分之一）并且会影响大脑（这是）。 难以治疗）目前尚无治愈方法，据我们所知，美国至少有五名患者。 Sanfilippo 患者组织在全球范围内登记了 19 个新增病例（请参阅支持信）。 Patricia Dickson 和 Tsui-Fen Chou 博士 (LABioMed) 开发了一种酶替代疗法 (ERT) 对于 MPS IIID，我们的策略建议提供重组人 α-N-乙酰氨基葡萄糖-6-硫酸酯酶。 (rhGNS) 通过脑室内输注有效治疗神经系统症状的根本原因 主导 MPS III 病理学的 ERT 可以对生活质量和患者发展产生巨大影响。 特别是在开发初期实施时，有几个成功的例子。 商业化的ERT（例如laronidase（MPS I）、idursulfase（MPS II）等）和BioMarin最近收到 批准针对巴顿病 CLN2 的 ERT 治疗 MPS I、II 和 IIIB 的其他 ERT 正在进行 I 期试验。 FDA和投资者都熟悉ERT及其商业化路径，这将大大增加 LABioMed 已申请 rhGNS 的美国专利，Phoenix Nest, Inc. 已申请了临床试验的机会。 我们的关键非临床和制造计划正在按计划进行。 我们与 FDA 进行了积极的互动，并获得了将我们的项目转移到诊所的指导。 为干预研究做准备，建议进行彻底的自然历史研究（NHS） 可用的患者群体具有广泛的网络来捕获最有可能预测临床的终点 由于确诊患者数量较少，因此收集的数据对每个人都有好处。 个体在干预时将是他们自己的对照，患者将接受重组 大部分工作将由合同服务提供商执行。 在刘博士的指导下在纽约大学进行，她拥有超过10项临床试验介入经验。 临床方案是由凤巢团队在 KOL 和临床的帮助下设计的。 我们聘请了专业的第三方临床服务提供商来帮助解决这一问题。 这项研究的执行、监测和数据收集将帮助我们。 开发临床结果，这将成为衡量 rhGNS 疗法疗效的工具，并将成为主要的 该试验的成功将使关键试验的执行更近一步。 评估我们的实验疗法及其商业化的功效。