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.

项目总结