McDonald Craig M, Marbán Eduardo, Hendrix Suzanne, Hogan Nathaniel, Ruckdeschel Smith Rachel, Eagle Michelle, Finkel Richard S, Tian Cuixia, Janas Joanne, Harmelink Matthew M, Varadhachary Arun S, Taylor Michael D, Hor Kan N, Mayer Oscar H, Henricson Erik K, Furlong Pat, Ascheim Deborah D, Rogy Siegfried, Williams Paula, Marbán Linda
University of California Davis School of Medicine, Sacramento, CA, USA.
Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Lancet. 2022 Mar 12;399(10329):1049-1058. doi: 10.1016/S0140-6736(22)00012-5.
Cardiosphere-derived cells (CDCs) ameliorate skeletal and cardiac muscle deterioration in experimental models of Duchenne muscular dystrophy. The HOPE-2 trial examined the safety and efficacy of sequential intravenous infusions of human allogeneic CDCs in late-stage Duchenne muscular dystrophy.
In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients with Duchenne muscular dystrophy, aged 10 years or older with moderate upper limb impairment, were enrolled at seven centres in the USA. Patients were randomly assigned (1:1) using stratified permuted blocks to receive CAP-1002 (1·5 × 10 CDCs) or placebo intravenously every 3 months for a total of four infusions. Clinicians, caregivers, patients, and clinical operations personnel were fully masked to treatment groups. The primary outcome was the change in mid-level elbow Performance of Upper Limb version 1.2 (PUL 1.2) score at 12 months, assessed in the intention-to-treat population. Safety was assessed in all individuals who received an investigational product. This trial is registered with ClinicalTrials.gov, NCT03406780.
Between March 1, 2018, and March 31, 2020, 26 male patients with Duchenne muscular dystrophy were enrolled, of whom eight were randomly assigned to the CAP-1002 group and 12 to the placebo group (six were not randomised due to screening failure). In patients who had a post-treatment PUL 1.2 assessment (eight in the CAP-1002 group and 11 in the placebo group), the mean 12-month change from baseline in mid-level elbow PUL1.2 favoured CAP-1002 over placebo (percentile difference 36·2, 95% CI 12·7-59·7; difference of 2·6 points; p=0·014). Infusion-related hypersensitivity reactions without long-term sequelae were observed in three patients, with one patient discontinuing therapy due to a severe allergic reaction. No other major adverse reactions were noted, and no deaths occurred.
CAP-1002 cell therapy appears to be safe and effective in reducing deterioration of upper limb function in patients with late-stage Duchenne muscular dystrophy. Various measures of cardiac function and structure were also improved in the CAP-1002 group compared with the placebo group. Longer-term extension studies are needed to confirm the therapeutic durability and safety of CAP-1002 beyond 12 months for the treatment of skeletal myopathy and cardiomyopathy in Duchenne muscular dystrophy.
Capricor Therapeutics.
在杜氏肌营养不良症的实验模型中，心肌球衍生细胞（CDC）可改善骨骼肌和心肌的退化。HOPE-2试验研究了晚期杜氏肌营养不良症患者序贯静脉输注人同种异体CDC的安全性和有效性。
在这项多中心、随机、双盲、安慰剂对照的2期试验中，年龄在10岁及以上、上肢中度受损的杜氏肌营养不良症患者在美国的7个中心入组。患者使用分层随机区组法按1:1随机分配，每3个月静脉注射CAP-1002（1.5×10个CDC）或安慰剂，共注射4次。临床医生、护理人员、患者和临床操作人员对治疗组完全不知情。主要结局是在意向性分析人群中，12个月时上肢功能1.2版（PUL 1.2）中级肘部评分的变化。对所有接受研究产品的个体进行安全性评估。本试验已在ClinicalTrials.gov注册，注册号为NCT03406780。
在2018年3月1日至2020年3月31日期间，26例男性杜氏肌营养不良症患者入组，其中8例随机分配至CAP-1002组，12例分配至安慰剂组（6例因筛查失败未随机分组）。在接受治疗后PUL 1.2评估的患者中（CAP-1002组8例，安慰剂组11例），中级肘部PUL1.2自基线起的12个月平均变化显示，CAP-1002组优于安慰剂组（百分位数差异36.2，95%CI 12.7-59.7；差异2.6分；p=0.014）。3例患者出现与输注相关的无长期后遗症的超敏反应，1例患者因严重过敏反应停止治疗。未观察到其他主要不良反应，也未发生死亡。
CAP-1002细胞疗法在降低晚期杜氏肌营养不良症患者上肢功能退化方面似乎是安全有效的。与安慰剂组相比，CAP-1002组的各种心脏功能和结构指标也有所改善。需要进行更长期的扩展研究，以确认CAP-1002在治疗杜氏肌营养不良症的骨骼肌病和心肌病方面超过12个月的治疗持久性和安全性。
Capricor Therapeutics公司。
