Long-acting Stable Glucagons for Treatment of Hyperinsulinism

长效稳定胰高血糖素治疗高胰岛素血症

基本信息

批准号：
10611746
负责人：
Pawel Fludzinski
金额：
$ 128.77万
依托单位：
AMIDEBIO, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-18 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10611746
关键词：
Animals Birth Blindness COVID-19 pandemic Canis familiaris Caregivers Cerebral Palsy Cessation of life Child Childhood Chronic Clinic Clinical Clinical Research Clinical Trials Complement Continuous Infusion Contracts DNA Sequence Alteration Defect Diabetes Mellitus Diffuse Disease Dose Effectiveness Epilepsy Equipment Event Failure Family Feedback Fermentation Formulation Glucagon Glucose Glucose Plasma Concentration Goals Grant Hyperinsulinism Hypoglycemia In Vitro Incidence Infusion Pumps Infusion procedures Investigational Drugs Investigational New Drug Application Lead Learning Disabilities Letters Life Medical Methods Mind Modeling Newborn Infant Operative Surgical Procedures Orphan Drugs Pancreatectomy Patient-Focused Outcomes Patients Persistent Hyperinsulinemia Hypoglycemia of Infancy Phase Phase II Clinical Trials Physiological Production Property Protocols documentation Pump Rattus Reporting Research Series Technology Testing Toxicology Tube United States United States National Institutes of Health Validation Work analog bariatric surgery base blood glucose regulation care costs cost design effective therapy immunogenicity in vitro Model in vitro activity in vivo in vivo evaluation insulin regulation insulin secretion large scale production lead candidate milligram mouse model novel patient population pharmacokinetics and pharmacodynamics phase 2 study phase II trial preference prevent primary endpoint programs rare condition scale up subcutaneous

项目摘要

SUMMARY/ABSTRACT In severe persistent hyperinsulinism (HI), repeated hypoglycemic episodes can ultimately lead to permanent seizure disorders, learning disabilities, cerebral palsy, blindness and even death. Clinical studies have demonstrated the effectiveness of both short-term and long-term treatment with glucagon for severe forms of HI and continuous subcutaneous administration of glucagon has been recommended both because of the potential improvement in patient outcome and high costs of surgical intervention followed by long-term annual care costs. However, the instability of native glucagon renders it inappropriate for chronic use in HI, and care-giver concerns about pump and infusion-tube blockage for stable glucagon analogs creates both administration problems and potential complications. In our redirected Phase II grant, we successfully discovered long-acting solution stable glucagon analogs suitable for treating HI, which would eliminate these concerns. In this Phase IIb project, we aim to further validate these lead analogs in HI mouse models, perform large scale (gram level) GLP production of the lead candidates to support the necessary toxicology, immunogenicity and formulation studies for an IND application. We also intend to pursue Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) prior to IND submission.

摘要/摘要在严重的持续性超胰岛素（HI）中，反复的降血糖发作最终会导致永久性癫痫发作，学习障碍，脑瘫，失明甚至死亡。临床研究表明，短期和长期治疗的有效性严重形式的HI和连续皮下给药的胰高血糖素已经是推荐既是由于患者结果的潜在改善和高成本的潜在改善手术干预，然后是长期的年度护理费用。但是，本地的不稳定胰高血糖素使其不适合在HI中长期使用，以及对泵和泵的担忧稳定胰高血糖素类似物的输液管阻塞既会产生给药问题，又会产生潜在的并发症。在我们重定向的第二阶段赠款中，我们成功地发现了长效溶液稳定的胰高血糖素类似物适合治疗HI，这将消除这些问题。在这个阶段IIB项目，我们旨在在HI鼠标模型中进一步验证这些铅类似物，执行大规模（克级）GLP生产铅候选者，以支持必要的毒理学，用于IND应用的免疫原性和制定研究。我们还打算追求孤儿在提交之前，药物名称（奇数）和罕见的小儿疾病名称（RPDD）。