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，而抗 炎症疗法在治疗这种情况下有着很大的希望。然而，慢的 疾病的进展性，患者数量少，发病和临床表现不同，缺乏 生物标记物的缺乏是骨密度药物开发的严重障碍。一种一流的类固醇，吸血鬼龙，有 显示出治疗Duchenne肌营养不良症的希望，并正在进行一项随机、 这一适应症的盲法对照验证性研究。在这个项目中，我们建议进行为期24周的试点试验 对30例2个部位BMD的门诊患者，每天6 mg/kg，评价其安全性和耐受性。 生物标志物、肌酸激酶、巨噬细胞衍生趋化因子和microRNA146a，以及计时10米 跑步/步行测试也将在整个试验过程中进行评估，以评估这些潜在治疗的有效性 骨密度患者对这种抗炎药物的反应生物标记物。如果艾美龙被证明是 安全性和耐受性在这项研究中，将计划进行一项治疗骨密度患者的对照研究。 药效学生物标志物的评价为临床用药提供客观依据 作用机制；如果在这项试点试验中有预期的变化，这些生物标记物将在 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.