Phase 2A Study of Exendin for the Treatment of Congenital Hyperinsulinism

Exendin 治疗先天性高胰岛素血症的 2A 期研究

• 批准号: 8568402
• 负责人: Diva D. De Leon
• 金额: $ 25.28万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8568402
• 关键词: Phase; 2A; Study; Exendin; Treatment

DESCRIPTION (provided by applicant): Congenital hyperinsulinism (CHI) is a rare genetic disorder of pancreatic beta-cell function characterized by failure to suppress insulin secretion in the presence of hypoglycemia, resulting in brain damage or death if inadequately controlled. Children affected by the most common form of CHI are unresponsive to medical therapy and require a near-total pancreatectomy shortly after birth for intractable hypoglycemia. Preliminary preclinical and clinical data suppor the use of the GLP-1 receptor antagonist, exendin-(9-39) as a novel therapeutic approach. The goal of this proposal is to obtain pharmacodynamics data for assessing the relationship between exendin-(9- 39) exposure and fasting blood glucose. The investigators propose two complimentary approaches to achieve this goal: 1) a clinical trial on the target population, and 2) a trial simulation. Aim 1 is an open label, placebo-controlled, single dose study to assess the effect, safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous exendin-(9-39) in children with CHI. Sixteen children 6 months of age and older with persistent hypoglycemia due to CHI will receive a six hour infusion of exendin-(9-39) or vehicle during fasting in a cross-over randomized design. The effect of treatment on blood glucose will be examined and pharmacokinetics and safety data will be collected. An exploratory aim will be to assess the immunogenicity of exendin-(9-39). The hypothesis is that exendin-(9-39) will elevate fasting blood glucose in a dose dependent manner and will be sufficiently well tolerated to permit continued clinical investigation. Aim 2 is a trial simulation to evaluate trial design constructs in an attempt to maximize the likelihood of clinical trial success for subsequent Phase 2/3 trials. The pharmacokinetics and pharmacodynamics data generated will be used for model-based prediction of doses and regimens expected to achieve target clinical endpoints for a future pivotal clinical trial.

描述（由申请人提供）： 先天性高胰岛素主义（CHI）是胰腺β细胞功能的罕见遗传疾病，其特征是在存在低血糖症的情况下未能抑制胰岛素分泌，如果不充分控制，会导致脑损伤或死亡。 受到最常见形式的CHI影响的儿童对医疗疗法无反应，并且需要在出生后不久就需要进行几乎完全的胰腺切除术才能治疗棘手的低血糖。 初步的临床前和临床数据支持GLP-1受体拮抗剂Exendin-（9-39）作为一种新型治疗方法。该提案的目的是获取药物学数据，以评估Exendin-（9-39）暴露与空腹血糖之间的关系。研究人员提出了两种免费的方法来实现这一目标：1）针对目标人群的临床试验； 2） 试验模拟。 AIM 1是一项开放标签，安慰剂对照的单剂量研究，可评估静脉注射肾上腺素（9-39）对CHI儿童的效果，安全性，耐受性，药代动力学和药效学。 6个月大的16名儿童因CHI而持续性低血糖，将在跨越随机设计的禁食过程中获得6小时的脱发（9-39）或车辆。将检查治疗对血糖的影响，并收集药代动力学和安全数据。探索性的目的是评估脱发的免疫原性（9-39）。假设是，Exendin-（9-39）将以剂量依赖性的方式升高空腹血糖，并将足够良好的耐受性以允许继续进行临床研究。 AIM 2是一个试验仿真，旨在评估试验设计构建体，以最大程度地提高随后的2/3阶段试验的临床试验成功可能性。生成的药代动力学和药效学数据将用于基于模型的预测剂量和预期的方案，以实现目标临床终点的未来关键临床试验。