A Pivotal Phase 3 Study of FCX-007 (Genetically-Modified Autologous Human Dermal Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa

FCX-007（转基因自体真皮成纤维细胞）治疗隐性营养不良性大疱性表皮松解症的关键 3 期研究

• 批准号: 10544379
• 负责人: Mary Spellman
• 金额: $ 50万
• 依托单位: CASTLE CREEK BIOSCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544379
• 关键词: Pivotal; Phase; Study; FCX; 007

7. PROJECT SUMMARY/ABSTRACT Recessive dystrophic epidermolysis bullosa (RDEB), is an autosomal recessive, inherited skin disease caused by mutations within the type VII collagen gene. The disease is characterized by painful blisters and wounds on skin and mucous membranes due to lack of adhesion of the epidermis to the inner dermal layers of the skin. The sequelae of wounds are often debilitating, disfiguring, and sometimes fatal. RDEB patients have a reduced life expectancy with early death resulting from infection, organ failure or squamous cell carcinoma (SCC). Current therapy for RDEB is limited to palliative wound care as there are currently no approved drugs for RDEB. Fibrocell Technologies, Inc. (FTI) is developing FCX-007, a suspension of live, ex-vivo, autologous human dermal fibroblast cells that have been genetically modified using a lentiviral vector (INXN-2004), which enables the expression of the human type VII (C7) protein. FTI has an open Investigational New Drug Application (IND 016582) for FCX-007. FTI proposes to continue its interventional, intra-patient randomized and controlled, open-label, Phase 3 study to evaluate the efficacy, durability, and safety of FCX-007. FTI has worked closely with the FDA in designing the Phase 3 clinical trial based on data gathered from the Phase 1/2 trial (FI-EB-001). Clinical efficacy will be determined by blinded investigator assessment of complete wound closure, durability of response, change in surface area of wound, and a patient reported outcome of pain. Clinical safety will be assessed by testing for presence of replication-competent lentivirus (RCL), type VII collagen autoantibody immune reactions, neoplasms (squamous cell carcinoma (SCC)), as well as physical examinations and adverse events (AEs). Efficacy and durability of FCX-007 will be assessed by the closure of wounds from Week 12 through Week 48, which FTI believes represents a clinically meaningful benefit to study subjects. FTI expects FCX-007 to be clinically safe given the FCX-007 Phase 1/2 clinical data (FI-EB-001), the preclinical safety data, and the autologous nature of the therapy. FCX-007 has been granted Orphan, Rare Pediatric Disease, and Regenerative Medicine Advanced Therapy (RMAT) designations by the FDA for the treatment of subjects with RDEB. The grant funding will be used to execute the Phase 3 clinical trial (FI-EB-002) which may lead to a potentially effective cell-based gene therapy for RDEB subjects. This grant proposal fulfills the goal of FDA's Office Orphan Product Development grant program to support the clinical development of products for use in rare diseases where no current therapy exists.

7. 项目概要/摘要 隐性营养不良性大疱性表皮松解症 (RDEB) 是一种常染色体隐性遗传性皮肤病 由 VII 型胶原蛋白基因突变引起的疾病。该病的特点是 由于缺乏粘连而导致皮肤和粘膜上出现疼痛的水泡和伤口 皮肤的表皮到真皮内层。伤口的后遗症常常使人衰弱， 毁容，有时甚至致命。 RDEB 患者预期寿命缩短且过早死亡 由感染、器官衰竭或鳞状细胞癌 (SCC) 引起。目前的治疗方法为 RDEB 仅限于姑息性伤口护理，因为目前没有批准用于 RDEB 的药物。 Fibrocell Technologies, Inc. (FTI) 正在开发 FCX-007，一种活体、离体、 使用慢病毒基因改造的自体人类真皮成纤维细胞 载体 (INXN-2004)，能够表达人类 VII 型 (C7) 蛋白。 FTI 有 FCX-007 的开放研究新药申请 (IND 016582)。 FTI 建议继续其介入性、患者内随机对照、开放标签、 评估 FCX-007 的功效、耐久性和安全性的 3 期研究。 FTI 已发挥作用 与 FDA 密切合作，根据收集的数据设计 3 期临床试验 1/2 期试验 (FI-EB-001)。临床疗效将由盲法研究者确定 评估伤口完全闭合、反应的持久性、伤口表面积的变化， 一名患者报告了疼痛的结果。临床安全性将通过测试是否存在来评估 有复制能力的慢病毒（RCL）、VII型胶原蛋白自身抗体免疫反应、 肿瘤（鳞状细胞癌（SCC）），以及体检和不良反应 事件（AE）。 FCX-007的功效和持久性将通过伤口闭合来评估 从第 12 周到第 48 周，FTI 认为这代表了具有临床意义的益处 学习科目。鉴于 FCX-007 1/2 期，FTI 预计 FCX-007 具有临床安全性 临床数据 (FI-EB-001)、临床前安全性数据以及治疗的自体性质。 FCX-007已获得孤儿药、罕见儿科疾病和再生医学奖 FDA 指定用于治疗 RDEB 受试者的高级疗法 (RMAT)。 赠款资金将用于执行 3 期临床试验 (FI-EB-002)，该试验可能会导致 针对 RDEB 受试者的潜在有效的基于细胞的基因疗法。本拨款提案满足 FDA 办公室孤儿产品开发资助计划的目标是支持临床 开发用于当前尚无治疗方法的罕见疾病的产品。