CSI Glucagon for Treatment of Congenital Hyperinsulinism

 描述(由申请人提供)：该计划的目标是进一步开发一种新的、稳定的非水高血糖素制剂--CSI(连续皮下输注)高血糖素(Tm)与Insulet OmniPod(R)输液泵相结合，用于预防先天性高胰岛素血症(HI)患者的低血糖。添加高血糖素将满足在治疗严重、持续性低血糖方面尚未得到满足的重大需求，并将使这一脆弱的儿科患者群体的血糖得到更好的控制。该计划旨在通过为期3个月的临床前研究来证明新型高血糖素的安全性，并在此基础上建立儿童HI患者的安全性和有效性。这项研究的主要临床指标将是CSI胰高血糖素(Tm)作为基础皮下输注维持正常血糖的能力。该项目的初步工作将制造临床用品，并将材料放在ICH稳定性测试计划中。之后，我们将在一个为期3个月的动物研究中评估CSI高血糖素(Tm)的安全性。然后，我们将向FDA提交研究新药(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儿童HI患者的第二阶段临床试验中进行评估。TRAL将需要对血糖稳定的患者进行3-6天的研究，然后进入门诊阶段，在此阶段，患者将继续使用CSI Glucagon(Tm)进行长达6个月的治疗，并每月进行检查。如果六个月后确定血糖得到了成功的控制，即他们每天的血糖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使用CSI GLucagon(Tm)治疗，直到孩子新陈代谢生长到他们的胰岛素产生。在这一点上，他们通常会摄入足够的复杂碳水化合物，以至于他们最终可能会停止治疗。这可以短到一年，但可以延长到五岁或更长时间。

 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.