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: 8839669
• 负责人: Diva D. De Leon
• 金额: $ 22.32万
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8839669
• 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）： 先天性高胰岛素血症 (CHI) 是一种罕见的胰腺 β 细胞功能遗传性疾病，其特征是在低血糖的情况下无法抑制胰岛素分泌，如果控制不当，会导致脑损伤或死亡。 受最常见形式的 CHI 影响的儿童对药物治疗没有反应，并且在出生后不久就需要因顽固性低血糖而进行近乎全胰腺切除术。 初步临床前和临床数据支持使用 GLP-1 受体拮抗剂 Exendin-(9-39) 作为一种新的治疗方法。该提案的目标是获得药效学数据，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互补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。目标 1 是一项开放标签、安慰剂对照、单剂量研究，旨在评估静脉注射 Exendin-(9-39) 对 CHI 儿童的疗效、安全性、耐受性、药代动力学和药效学。在交叉随机设计中，16 名 6 个月及以上因 CHI 导致持续低血糖的儿童将在禁食期间接受 6 小时输注 exendin-(9-39) 或载体。将检查治疗对血糖的影响，并收集药代动力学和安全性数据。探索性目标是评估 exendin-(9-39) 的免疫原性。假设 exendin-(9-39) 将以剂量依赖性方式升高空腹血糖，并且具有足够良好的耐受性以允许继续进行临床研究。目标 2 是一项试验模拟，旨在评估试验设计结构，以最大限度地提高后续 2/3 期试验临床试验成功的可能性。生成的药代动力学和药效学数据将用于基于模型的剂量和治疗方案预测，以实现未来关键临床试验的目标临床终点。