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.

项目摘要 Sanfilippo疾病（粘膜近代糖尿病III型； MPS III）是一种毁灭性的神经培养性溶酶体 童年的储存障碍，其病理特征是神经系统的：发育的放缓，严重 行为问题，渐进性认知能力下降，痴呆和运动技能的下降导致不动， 无反应和死亡。 乙酰葡萄糖6-硫酸酯酶（GNS）。 可以治疗的difficalt）没有治疗或治疗，据我们所知，美国至少有五名患者。 Sanfilippo Patiance组织在世界各地还注册了19个Casses（请参阅支持信）。 Patricia Dickson和Tsui-Fen Chou博士（Labiomed）开发了一种酶替代处理（ERT） 对于MPS IIID。 （RHGNS）通过室内注入式输注对神经系统症状的病因进行培训 主导MPS III病理学。 尤其是在开发初期管理的 最近收到的商业化ERT（例如Laronidase（MPS I），IDursulfase（MPS II）等）和BioMarin最近收到 批准ERT用于Batten疾病的形式，CLN2。 FDA和投资者都熟悉ERT及其通讯道路，这将大大增加您的状态 进行临床试验的机会 许可我们的关键非临床和制造计划。 我们与FDA有积极的互动，并获得了将我们的计划转移到诊所的指导 介入研究的准备建议是针对一项彻底的自然历史研究（NHS） 可用的患者人群具有广泛的网络以捕获最有可能预测临床的端点 每个人都受益。 在干预时，个人将是自己的控制 酶。 在Lau博士的指导下，在纽约大学进行了10次临床试验的经验 和观测。 MPS III领域的专家。我们有英国专家第三方临床服务。 执行，监视和数据收集。 开发临床结果，这将是测量我们RHGHNS治疗功效的工具将是主要的 关键研究的终点。 评估我们的实验疗法的功效，并且是商业化。