Pilot Trial of Vamorolone for the Treatment of Becker Muscular Dystrophy

瓦莫洛龙治疗贝克尔肌营养不良症的初步试验

• 批准号: 10437669
• 负责人: Paula R Clemens
• 金额: $ 14.03万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-13 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437669
• 关键词: 3' Untranslated Regions; Address; Anti-Inflammatory Agents; Becker Muscular Dystrophy; Binding; Biological Markers; Blinded; Bone Density; Chronic; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Complex; Controlled Study; Creatine Kinase; Data; Disease; Dose; Duchenne muscular dystrophy; Dystrophin; Evaluation; FDA approved; Future; Genetic; Genetic Transcription; Glucocorticoids; Inflammation; Intervention; Label; Measures; Membrane; Messenger RNA; MicroRNAs; Mineralocorticoids; Muscle; Muscular Atrophy; Myopathy; Natural Immunity; Nature; Neuromuscular Diseases; Osteocalcin; Outcome; Pathologic Processes; Pathology; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Production; Publishing; Randomized; Research Design; Role; Running; Safety; Serum; Site; Skeletal Muscle; Steroids; Study of serum; Supportive care; Testing; Therapeutic; Time; Walking; antagonist; biomarker validation; bone geometry; bone health; bone turnover; boys; candidate marker; clinical care; design; drug development; drug mechanism; efficacy evaluation; functional outcomes; improved; macrophage-derived chemokine; meter; novel; open label; pharmacodynamic biomarker; phase 2 testing; phase III trial; pilot test; pilot trial; potential biomarker; programs; protein expression; response; safety testing; side effect; therapy design; treatment effect

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.

项目摘要 贝克尔肌肉营养不良（BMD）和抗 - 炎症疗法对治疗这种疾病的患者有很大的希望。但是，慢 疾病的渐进性，少数患者，可变发作和临床表现以及缺乏 生物标志物在BMD中呈现出严重的药物开发障碍。一流的类固醇Vamorolone具有 显示出对患有杜尚肌营养不良症的年轻男孩的治疗的希望 该指示的盲目和受控的验证性研究。在这个项目中，我们提出了24周的试点试验 30名AMBD患者的Vamorolone 6 mg/kg/day在2个地点，可评估安全性和耐受性。 生物标志物，肌酸激酶，巨噬细胞衍生的趋化因子和microRNA 146a，定时10米 在整个试验中还将评估跑步/步行测试，以评估这些潜在治疗的有用性 对BMD患者的这种抗炎药的反应生物标志物。如果证明瓦莫洛龙是 在这项研究中，将计划对BMD患者的Vamorolone治疗进行对照研究。 在这项短期试验中对药效生物标志物的评估旨在为药物提供客观证据 作用机理；如果预计该试验试验会发生变化，则将进一步研究这些生物标志物 下一个阶段试验。