3147K2-101-WW: A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, MULTIPLE ASCENDY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。主要目的是评估MYO-029在成年肌肉萎缩症患者中的安全性。次要目标是(1)通过评估肌肉质量、体积、力量和组织病理学来评估MYO-029在成年肌肉萎缩症患者中的生物活性；patient-reported结果;功能测量；(2)探索基因表达模式、试验品给药和临床参数之间的关系；(3)评估MYO-029在成年MD患者中的药代动力学。这是一项随机、双盲、安慰剂对照、多次递增剂量的安全性研究。大约136名受试者将被分配到1至4个顺序剂量队列（队列1和2各36名受试者，队列3和4各32-36名受试者）。队列1- 1mg /kg的MYO-029或安慰剂组2- 3mg /kg的MYO-029或安慰剂组3- 10mg /kg的MYO-029或安慰剂组4- 30mg /kg的MYO-029或安慰剂组每2周接受一次试验品，共13次。每个队列将纳入同等数量的BMD、FSHD和LGMD受试者。本研究中的安慰剂设计元素将为MYO-029在给定研究人群中的安全性、耐受性和药理活性方面无药物效应提供参考。双盲设计与安慰剂对照相结合，将为研究提供保护，防止研究者或受试者在研究评估中引入偏倚。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective is to evaluate the safety of MYO-029 in adult subjects with muscular dystrophy. The secondary objectives are to (1) evaluate the biological activity of MYO-029 in adult subjects with muscular dystrophy by evaluating muscle mass, volume, strength, and histopathology; patient-reported outcome; and functional measurements; (2) explore associations between gene expression patterns, test article administration, and clinical parameters, and (3) evaluate the pharmacokinetics of MYO-029 in adult subjects with MD. This is a randomized, double blind, placebo-controlled, multiple ascending dose, safety study. Approximately 136 subjects will be assigned to 1 to 4 sequential dose cohorts 936 subjects each in Cohort 1 and 2 and 32-36 subjects each in cohort 3 and 4). Cohort 1- 1 mg/kg MYO-029 or placebo Cohort 2- 3 mg/kg MYO-029 or placebo Cohort 3- 10 mg/kg MYO-029 or placebo Cohort 4- 30 mg/kg MYO-029 or placebo Each subject will receive test article once every 2 weeks for a total of 13 doses. Equal numbers of subjects with BMD, FSHD, and LGMD will be enrolled in each cohort. The placebo design element in this study will provide a reference for no drug effects with respect to the safety, tolerability, and pharmacological activity of MYO-029 for the given study population. A double-blind design employed in conjunction with a placebo control will provide the study with protection against introduction of a bias into the study evaluation either by the investigatory or the subjects.