From The Heart Institute (M.T., J.J., B.G.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center (B.B.), and Division of Pediatric Cardiology, Congenital Heart Center (J.F.), University of Florida, Gainesville; Department of Cardiology (J.L., B.A.-V., M.R.O.), Johns Hopkins University, Baltimore, MD; Smidt Heart Institute (R.M., E.M., R.G.V.), Cedars-Sinai Medical Center, Los Angeles, CA; Capricor Therapeutics (R.R.S., B.F., J.R., J.M.P., L.M., D.D.A.), Beverly Hills, CA; and Department of Cardiology (K.M.), Laikon Hospital, Athens, Greece.
Neurology. 2019 Feb 19;92(8):e866-e878. doi: 10.1212/WNL.0000000000006950. Epub 2019 Jan 23.
To assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).
The Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Participants were enrolled at 3 US medical centers between January and August 2016 and followed for 12 months. An independent Data and Safety Monitoring Board provided safety oversight. Cardiac function and structure were assessed by MRI, and analyzed by a blinded core laboratory. Skeletal muscle function was assessed by performance of the upper limb (PUL).
Twenty-five eligible patients (mean age 17.8 years; 68% wheelchair-dependent) were randomized to CAP-1002 (n = 13) or control (n = 12). Incidence of treatment-emergent adverse events was similar between groups. Compared to baseline, MRI at 12 months revealed significant scar size reduction and improvement in inferior wall systolic thickening in CAP-1002 but not control patients. Mid-distal PUL improved at 12 months in 8 of 9 lower functioning CAP-1002 patients, and no controls ( = 0.007).
Intracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months. Thus, future clinical research on CAP-1002 treatment of DMD cardiac and skeletal myopathies is warranted.
This phase I/II study provides Class II evidence that for patients with DMD, intracoronary CAP-1002 is feasible and appears safe and potentially effective.
评估冠状动脉内异体心脏球源性细胞（CAP-1002）治疗杜氏肌营养不良症（DMD）患者的可行性、安全性和疗效。
Halt 心肌病进展（HOPE）-杜氏肌营养不良症试验是一项 I/II 期、随机、对照、开放标签试验（NCT02485938）。入选年龄>12 岁、心肌纤维化程度较重的 DMD 患者，按 1:1 随机分配至常规治疗（对照组）或冠状动脉内全容积输注 CAP-1002（7500 万细胞）。2016 年 1 月至 8 月，3 家美国医疗中心共纳入 25 例符合条件的患者，并随访 12 个月。独立的数据和安全监测委员会对安全性进行监测。心脏功能和结构通过 MRI 评估，并由一个盲法核心实验室进行分析。骨骼肌功能通过上肢功能（PUL）进行评估。
共纳入 25 例符合条件的患者（平均年龄 17.8 岁，68%需坐轮椅），随机分配至 CAP-1002 组（n=13）或对照组（n=12）。两组治疗相关不良事件发生率相似。与基线相比，12 个月时 MRI 显示 CAP-1002 组而非对照组患者的疤痕面积显著缩小，下壁收缩增厚改善。12 个月时，8 例 CAP-1002 患者的上肢功能得到改善，而对照组无改善（=0.007）。
冠状动脉内输注 CAP-1002 治疗 DMD 似乎是安全的，在心脏和上肢功能方面，12 个月时显示出疗效信号。因此，有必要开展 CAP-1002 治疗 DMD 心脏和骨骼肌疾病的临床研究。
这项 I/II 期研究提供了 II 级证据，表明对于 DMD 患者，冠状动脉内输注 CAP-1002 是可行的，且安全、可能有效。
