The Phase I/II Randomized, Prospective, Double-blinded, Sham-controlled Cross-over Study of Intravitreal Autologous Bone Marrow CD34+ Stem Cell Therapy for Retinal Vein Occlusion

项目总结： 这一I/II阶段的目标是前瞻性、随机、假对照、双盲 临床试验是确定玻璃体内自体CD34+细胞治疗是否安全、可行 对视网膜静脉阻塞(RVO)导致视力丧失的眼睛有潜在的益处。RVO是一种 导致老年人视力丧失的主要原因是视网膜血管。人骨髓中的CD34+细胞 在组织缺血时被动员到循环中进行组织血运重建和 修理。由于CD34+细胞的局部输送有利于缺血组织，玻璃体内输送 CD34+细胞可能对RVO患者的视力和视网膜缺血有促进作用。一项试点临床试验已经完成 使用玻璃体内自体CD34+骨髓没有重大的安全性或可行性问题 细胞。在这项扩展的I/II期研究中，15名患有持续性视力丧失的受试者(15只眼) RVO将被录取，并将持续2年。总学习时间为60个月。这首单曲- 中心研究将在加州大学戴维斯分校进行。协调中心将设在 埃默斯公司。研究主席/首席研究员将由苏珊娜·朴博士担任。这项研究 将在FDA批准的IND下进行。数据和安全监测委员会将 监督这项研究。受试者将以2：1的比例随机分配到细胞疗法或 假/延期细胞疗法。细胞疗法包括骨髓抽吸，分离 抽吸物中的CD34+细胞在良好的制造实践条件下，以及玻璃体内 注射分离的CD34+细胞。假治疗包括假骨髓抽吸术和 玻璃体内注射，不穿透骨骼或眼睛。主题，审视 眼科医生和视力检查员将继续戴面具研究治疗 随机化到第六个月。此后，这项研究将被揭开面纱，并进行假治疗 受试者将接受骨髓抽吸和细胞治疗。全面的眼光 ETDRS最佳矫正视力检查，光学相干断层扫描，自动 荧光、眼底照相、荧光素血管造影术、微视野和 视网膜电描记术将在基线和连续进行。主要结果衡量标准 将是与细胞相关的眼部和全身不良事件的发生率和严重性 治疗和注射分离的CD34+细胞的数量。次要结果衡量标准 将是细胞治疗后视觉功能、视网膜血流和形态的变化。 长期目标是确定玻璃体内自体CD34+细胞疗法是否可以 在不影响安全性的情况下，最大限度地减少或逆转与视网膜缺血相关的视力损失。

Project Summary: The goal of this phase I/II prospective, randomized, sham-controlled, double-blinded clinical trial is to determine whether intravitreal autologous CD34+ cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from retinal vein occlusion (RVO). RVO is a leading retinal vascular cause of vision loss in the elderly. CD34+ cells in human bone marrow are mobilized into the circulation in response to tissue ischemia for tissue revascularization and repair. Since local delivery of CD34+ cells benefits ischemic tissue, intravitreal delivery of CD34+ cells may benefit vision and retinal ischemia in eyes with RVO. A pilot clinical trial has shown no major safety or feasibility concerns using intravitreal autologous CD34+ bone marrow cells. In this expanded phase I/II study, 15 subjects (15 eyes) with persistent vision loss from RVO will be enrolled and follow for 2 years. Total study duration will be 60 months. This single- center study will be at the University of California Davis. The Coordinating Center will be Emmes Corporation. The Study Chair/Principal Investigator will be Dr. Susanna Park. The study will be conducted under an IND cleared from FDA. A Data and Safety Monitoring Committee will oversee the study. Subjects will be randomized at enrollment 2:1 to cell therapy or sham/deferred cell therapy. The cell therapy involves bone marrow aspiration, isolation of CD34+ cells from the aspirate under Good Manufacturing Practice conditions, and intravitreal injection of isolated CD34+ cells. Sham therapy involves sham bone marrow aspiration and intravitreal injection without penetrating the bone or eye. The subject, examining ophthalmologist and visual acuity examiner will remain masked to study treatment randomization till month six. Thereafter, the study will be unmasked and the sham-treated subjects will undergo bone marrow aspiration and cell therapy. A comprehensive eye examination with ETDRS best-corrected visual acuity, optical coherence tomography, auto- fluorescence, fundus photography, fluorescein angiography, microperimetry and electroretinography will be performed at baseline and serially. The primary outcome measures will be the incidence and severity of ocular and systemic adverse events associated with cell therapy and the number of CD34+ cells isolated for injection. The secondary outcome measures will be the changes in visual function, retinal perfusion and morphology following cell therapy. The long-term objective is to determine whether intravitreal autologous CD34+ cell therapy can minimize or reverse vision loss associated with retinal ischemia without compromising safety.