Data from: Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial

Objective: To assess the feasibility, safety, and efficacy of
intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients
with Duchenne muscular dystrophy (DMD). Methods: 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).
Results: 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 (p = 0.007).
Conclusions: 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. Classification of evidence:
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.

研究目的：评估冠状动脉内输注同种异体心肌球来源细胞（cardiosphere-derived cells, CAP-1002）用于杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）患者的可行性、安全性与有效性。
研究方法：本研究为抑制心肌病进展（Halt Cardiomyopathy Progression, HOPE）-Duchenne试验，属于I/II期随机对照开放标签临床试验（临床试验注册号：NCT02485938）。纳入年龄＞12岁、存在显著心肌纤维化的DMD患者，按1:1比例随机分配至常规治疗对照组，或CAP-1002冠状动脉内全域输注组（细胞剂量为7500万个）。研究于2016年1月至8月在美国3家医学中心招募受试者，随访周期为12个月。独立数据与安全监查委员会负责全程安全性监查。采用磁共振成像（Magnetic Resonance Imaging, MRI）评估心脏结构与功能，由设盲的核心实验室完成数据分析。上肢功能评估采用上肢性能测试（Performance of Upper Limb, PUL）。
研究结果：共计25名符合入组标准的患者（平均年龄17.8岁；68%需依赖轮椅）被随机分配至CAP-1002组（n=13）与对照组（n=12）。两组治疗期间出现的不良事件发生率无显著差异。与基线水平相比，CAP-1002组患者在随访12个月时的MRI结果显示心肌瘢痕面积显著缩小，下壁收缩增厚功能得到改善，而对照组未出现上述变化。在9名基础功能较低下的CAP-1002组患者中，有8名患者的中远端上肢功能在12个月时得到改善，对照组则无此类改善（p=0.007）。
研究结论：冠状动脉内输注CAP-1002用于DMD患者的治疗具备可行性，且安全性良好，在长达12个月的随访周期内显示出对心脏功能与上肢功能的改善信号。因此，后续针对CAP-1002治疗DMD相关心脏及骨骼肌病变的临床研究具有开展价值。
证据分类：本项I/II期研究提供了II类证据，表明对于DMD患者，冠状动脉内输注CAP-1002具备可行性，且安全性良好，潜在有效性显著。