Phase IIa study of VBP15 for Duchenne muscular dystrophy

 描述（由申请人提供）：ReveraGen BioPharma是一家临床阶段药物开发公司，正在开发VBP 15，一种新型游离甾体类药物。发展的最初适应症是杜氏肌营养不良症，其中VBP 15有望保留或增加糖皮质激素的功效，同时减少副作用（骨脆弱，生长发育迟缓）。VBP 15目前正在成人志愿者中进行I期临床试验。这项拟议的II期SBIR研究是在杜氏肌营养不良症男孩中进行IIa期临床试验，类固醇初治，年龄4-7岁。目的1是在多次递增剂量（MAD）试验设计中测试VBP 15的四个剂量水平，用药两周。完成IIa期临床试验的患者将被纳入为期6个月的扩展研究。目的是在IIa期临床试验中检验儿科药代动力学、耐受性和安全性，并在6个月扩展研究中评估疗效（至站立速度的时间）和安全性（体重指数的变化），以帮助未来IIb期注册试验中的剂量选择。目的2：开发一种药效学生物标志物组，可以评估外周血急性时间范围内的安全性和有效性标志物。我们已经使用SomaScan和蛋白质组学发现方法完成了DMD血清生物标志物的自然史，并提供了糖皮质激素相关疗效和安全性生物标志物的初步数据。II期SBIR研究将比较VBP 15生物标志物与糖皮质激素生物标志物，作为评估比较安全性和潜在疗效的方法。

 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.