Phase IIa study of VBP15 for Duchenne muscular dystrophy

 描述(申请人提供)：ReveraGen BioPharma是一家临床阶段药物开发公司，正在开发一种新型解离类固醇类药物VBP15。最初的发展指征是杜氏肌营养不良症，VBP15有望保留或增加糖皮质激素的疗效，同时减少副作用(骨骼脆化、生长迟缓)。VBP15目前正处于成人志愿者的I期临床试验中。这项拟议的第二阶段SBIR研究将对4-7岁的Duchenne肌营养不良症男孩进行IIa期临床试验，类固醇天真。目标1是在多个递增剂量(MAD)试验设计中测试VBP15的四个剂量水平，药物治疗两周。完成IIa期临床试验的患者将被允许参加六个月的延期研究。目标是在IIa期临床试验中测试儿科药物动力学、耐受性和安全性，并在6个月的扩展研究中评估疗效(站立速度时间)和安全性(体重指数变化)，以帮助在未来的IIb期登记试验中进行剂量选择。目的：建立一种药效学生物标志物小组，用于评估急性时间段外周血的安全性和有效性标志物。我们使用SomaScan和蛋白质组学发现方法完成了DMD血清生物标记物的自然历史，并提供了糖皮质激素相关疗效和安全性生物标记物的初步数据。第二阶段的SBIR研究将比较VBP15生物标记物和糖皮质激素生物标记物，作为评估相对安全性和潜在疗效的一种手段。

 DESCRIPTION (provided by applicant): ReveraGen BioPharma is a clinical stage drug development company that is developing VBP15, a novel dissociative steroidal class drug. The initial indication for development is Duchenne muscular dystrophy, where VBP15 holds promise for retaining or increasing efficacy of glucocorticoids, while reducing side effects (bone fragilit, stunting of growth). VBP15 is currently in Phase I clinical trials in adult volunteers. This proposed Phase II SBIR research is to carry out a Phase IIa clinical trial in Duchenne muscular dystrophy boys, steroid naïve, ages 4-7 yrs. Aim 1 is to test four dose levels of VBP15 in a multiple ascending dose (MAD) trial design, with two weeks on drug. Patients completing the Phase IIa clinical trial will be offered enrollment into a six month extension study. The goal is t test pediatric pharmacokinetics, tolerability and safety in the Phase IIa clinical trial, and assessments of efficacy (time to stand velocity) and safety (change in body mass index) in the six month extension study to aid dose selection in the future Phase IIb registration trial. Aim 2 i to develop a pharmacodynamics biomarker panel that can assess safety and efficacy markers in acute time frames from peripheral blood. We have completed a natural history of DMD serum biomarkers using both SomaScan and proteomics discovery methods, and present preliminary data on glucocorticoid- associated efficacy and safety biomarkers. The Phase II SBIR research will compare VBP15 biomarkers to glucocorticoid biomarkers as a means of assessing comparative safety and potential efficacy.