CLINICAL TRIAL: PHASE I TRIAL OF INTRAMUSCULAR INJECTION OF RAAV1-CB-HAAT

临床试验：RAAV1-CB-HAAT 肌内注射 I 期试验

• 批准号: 7950715
• 负责人: MARK Louis BRANTLY
• 金额: $ 1.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950715
• 关键词: Animal Model; Biological Assay; Capsid; Chemistry; Chickens; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Data; Dependovirus; Dose; Enhancers; Funding; Genes; Grant; Hematology; Human; Hybrids; Immunologics; Institution; Intramuscular; Intramuscular Injections; Measurement; Mus; Patients; Phase; Phase I Clinical Trials; Pulmonary function tests; Recombinant adeno-associated virus (rAAV); Recording of previous events; Reporting; Research; Research Personnel; Resources; Safety; Seminal fluid; Serotyping; Serum; Source; Symptoms; United States National Institutes of Health; Urinalysis; alpha 1-Antitrypsin; beta Actin; human subject; meetings; open label; promoter; recombinant virus; response; vector; vector genome

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. A recombinant virus vector was constructed from adeno associated virus-AAV that has been altered to carry the human alpha 1-antitrypsin-hAAT gene expressed from a hybrid chicken beta actin promoter with a cytomegalovirus enhancer. This construct has been shown to express hAAT in animal models closely matching the proposed human trial. Our group is currently performing a phase I safety and dose-finding study of a recombinant adeno-associated virus serotype 2-rAAV2-AAT vector given by intramuscular-IM administration to Alpha 1-Antitrypsin Deficient-AATD patients. Mouse data suggests that this same rAAV-AAT gene cassette will produce much higher serum levels of AAT if it is packaged in an AAV serotype 1 pseudotyped capsid. This proposed clinical trial is an open label, phase I study administering rAAV1-CB-hAAT gene vector intramuscularly to AAT deficient human subjects who meet entry criteria. It will cover the same dose range as the current rAAV2-AAT study- approximately 2x1012 to 6.9x1013 vector genomes per patient. Safety parameters will be measurement of changes, in serum chemistries and hematology, urinalysis, pulmonary function testing, semen assay for vector genomes, immunologic response to AAT and AAV, as well as reported subject history of any symptoms.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 重组病毒载体是由Adeno相关病毒-AAV构建的，该病毒载体已被改变，以携带由杂化鸡β肌动蛋白启动子和巨细胞病毒增强剂表达的人alpha 1-抗抗蛋白酶-HAAT基因。已显示该构造在动物模型中表达与拟议人类试验密切相匹配的动物模型。目前，我们的小组正在进行I期安全和剂量调查研究，对由肌内IM给药对α1-抗抗蛋白酶缺乏 - AATD患者的重组腺相关病毒血清2-RAAV2-AAT载体进行。 鼠标数据表明，如果将其包装在AAV血清型1伪分型的帽子中，则相同的RAAV-AAT基因盒将产生更高的血清AAT水平。 该拟议的临床试验是一项开放标签，I期研究对符合进入标准的AAT缺乏的人类受试者进行肌肉内施用RAAV1-CB-HAAT基因载体。 它将覆盖与当前RAAV2-AAT研究相同的剂量范围 - 每个患者约为2x1012至6.9x1013载体基因组。 安全参数将是测量变化，血清化学和血液学，尿液分析，肺功能测试，载体基因组的精液测定，对AAT和AAV的免疫学反应以及任何症状的主题病史。