Pilot Trial of Vamorolone for the Treatment of Becker Muscular Dystrophy

项目摘要 贝克肌营养不良症（BMD）患者迫切需要新的治疗方法， 炎症疗法对于治疗患有这种病症的患者具有很大的希望。然而，缓慢 疾病的进行性，患者人数少，发病和临床表现多变，缺乏 生物标志物的缺乏是骨密度药物开发的一个严重障碍。一流的类固醇，vamorolone， 显示出治疗杜氏肌营养不良症的年轻男孩的希望， 该适应症的设盲和对照验证性研究。在这个项目中，我们建议进行为期24周的试点试验， 在30名具有2个部位BMD的非卧床患者中，vamorolone 6 mg/kg/天，评价安全性和耐受性。 生物标志物、肌酸激酶、巨噬细胞衍生的趋化因子和microRNA 146 a，以及定时10米 还将在整个试验期间评价跑步/步行试验，以评估这些潜在治疗的有效性 BMD患者对这种抗炎药物的反应性生物标志物。如果证实瓦莫龙 安全和可耐受的，在这项研究中，将计划对BMD患者进行伐莫龙治疗的对照研究。 在这项短期试验中，药效学生物标志物的评价为药物治疗提供了客观证据。 作用机制;如果在该初步试验中预期会发生变化，则将进一步研究这些生物标志物， 下一阶段的试验。

Project Summary Novel treatments are desperately needed by patients with Becker muscular dystrophy (BMD), and anti- inflammatory therapies hold great promise for treating patients with this condition. However, the slow progressive nature of the disease, small numbers of patients, variable onset and clinical presentation, and lack of biomarkers presents a serious barrier to drug development in BMD. A first-in-class steroid, vamorolone, has shown promise for the treatment of young boys with Duchenne muscular dystrophy and is in a randomized, blinded and controlled, confirmatory study for this indication. In this project, we propose a 24-week pilot trial of vamorolone 6 mg/kg/day in 30 ambulatory patients with BMD at 2 sites, evaluating safety and tolerability. Biomarkers, creatine kinase, macrophage derived chemokine, and microRNA 146a, and the timed 10 meter run/walk test will also be evaluated throughout the trial, to assess the usefulness of these potential treatment responsive biomarkers to this anti-inflammatory drug in BMD patients. If vamorolone is demonstrated to be safe and tolerable in this study, a controlled study of vamorolone treatment for BMD patients will be planned. Evaluation of pharmacodynamic biomarkers in this short trial serves to provide objective evidence for drug mechanism of action; if there is expected change in this pilot trial, these biomarkers would be further studied in the next phase trial.