Gene Therapy for Congenital Adrenal Hyperplasia through Administration of an Adeno-Associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2

通过使用编码人 CYP21A2 的腺相关病毒 (AAV) 血清型 5 重组载体进行先天性肾上腺增生症的基因治疗

• 批准号: 10691784
• 负责人: Deborah Merke
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10691784
• 关键词: 21-hydroxylase deficiency; Adenovirus Vector; Adrenal Glands; Adult; Age; Animals; Biodistribution; CYP21A2 gene; Cardiovascular Diseases; Cessation of life; Clinical Trials; Congenital adrenal hyperplasia; Dependovirus; Diagnosis; Dose; Human; Incidence; Injections; Lead; Life; Longevity; Mendelian disorder; Metabolic Diseases; Monitor; Mus; Participant; Patients; Phase; Phenotype; Quality of life; Recombinants; Research Design; Risk; Safety; Serotyping; Shock; Steroid 21-Monooxygenase; Steroid biosynthesis; Time; Weight Gain; adeno-associated viral vector; base; clinical development; design; effective therapy; efficacy evaluation; enzyme activity; expression vector; first-in-human; gene therapy; human study; intravenous injection; mortality; nonhuman primate; open label; pre-clinical; programs; safety assessment; sex; standard of care; vector; vector genome

As a monogenic disease, congenital adrenal hyperplasia due to 21-hydroxylase deficiency is amenable to genetic interventions. Promising pre-clinical programs have led to a first-in-human clinical trial. This is a Phase 1/2, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of an AAV5 based gene therapy administered to up to 25 adult participants diagnosed with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. All participants who receive gene therapy will be closely monitored for one year and followed for a minimum of an additional four years for safety and efficacy.

作为一种单基因疾病，21-羟化酶缺乏导致的先天性肾上腺增生症适合遗传干预。 有前景的临床前项目已经进行了首次人体临床试验。这是一项 1/2 期、开放标签、剂量递增研究，旨在评估基于 AAV5 的基因疗法的安全性、耐受性和有效性，该疗法对最多 25 名被诊断患有因 21-羟化酶缺乏症导致的典型先天性肾上腺增生症的成年参与者进行治疗。所有接受基因治疗的参与者都将受到为期一年的密切监测，并至少再随访四年，以确保安全性和有效性。