CSI Glucagon for Treatment of Congenital Hyperinsulinism

 描述（由申请方提供）：本项目旨在进一步开发一种新型、稳定的非水性胰高血糖素制剂- CSI（连续皮下输注）胰高血糖素（tm）联合Insulet OmniPod（r）输注泵，用于预防先天性高胰岛素血症（HI）患者的低血糖症。添加胰高血糖素将满足重度、持续性低血糖管理中显著未满足的需求，并将允许更好地控制该脆弱儿科患者人群的血糖。该项目旨在通过3个月临床前研究证明新型胰高血糖素的安全性，并在此后确定其在HI儿科患者中的安全性和疗效。本研究的主要临床指标将是CSI胰高血糖素（TM）维持正常血糖的能力，以基础皮下输注的形式输送。本项目的初始工作将生产临床供应品，并将材料纳入ICH稳定性试验计划。此后，我们将在为期3个月的动物研究中评估CSI Glucagon（tm）的安全性。然后，我们将向FDA提交研究性新药（IND）申请。最后，我们的可溶性胰高血糖素的安全性和有效性将在HI儿科患者的II期临床试验中进行评估。一旦患者通过葡萄糖稳定，tral将需要在患者中进行3-6天的研究，此后进入门诊期，其中患者将继续使用CSI胰高血糖素（tm）治疗长达6个月，每月进行检查。如果六个月后确定血糖得到成功控制，即，如果他们每天保持在正常的血糖范围内，父母将可以选择让他们的孩子继续用CSI胰高血糖素TM治疗，直到孩子在代谢上“生长”到他们的胰岛素产生。在这一点上，他们通常消耗足够的复合碳水化合物，使得他们最终可以停止治疗。这可以短至1年，但可以延长至5岁或更长时间。

 DESCRIPTION (provided by applicant): The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation - CSI (continuous subcutaneous infused) Glucagon(tm) in combination with a Insulet OmniPod(r) infusion pump for prevention of hypoglycemia in patients with congenital hyperinsulinism (HI). The addition of glucagon will meet a significant unmet need in the management of severe, persistent hypoglycemia and will allow greater control of blood glucose in this fragile pediatric patient population. This program intends to demonstrate the safety of the novel glucagon in a 3-month preclinical study and thereafter, establish safety and efficacy in pediatric patients with HI. The major clinical metric for this study will be the ability of CSI Glucagon(tm) to maintain normoglycemia, delivered as a basal subcutaneous infusion. The initial effort of this project will manufacture clinical supplies and put material on an ICH stability testing program. Thereafter, we will assess of the safety of CSI Glucagon(tm) in a 3-month animal study. Then, we will file an Investigational New Drug (IND) application with the FDA. Finally, the safety and efficacy of our soluble glucagon will be assessed in a Phase 2 clinical trial in pediatric patients with HI. The tral will entail a 3-6 day study in patients once they are stabilized with glucose and thereafter an outpatient phase, wherein patients will continue therapy with CSI Glucagon(tm) for a period of up to six months with monthly examinations. If after six months it is determined that blood glucose is being successfully managed i.e., they remain in a normal glycemic range on a daily basis, the parents will have the option to have their child continue treatment with CSI Glucagon(tm) until such time that the child metabolically "grows into" their insulin production. At this point, they ae typically consuming sufficient complex carbohydrates such that they can eventually discontinue treatment. This can be as short as 1 year, but can extend up to 5 years of age or longer.