Darvadstrocel in Patients With Crohn's Disease With Complex Perianal Fistulas: The ADMIRE CD II Phase 3 Randomized Trial.

The efficacy and safety of darvadstrocel in an expanded patient population was investigated.

研究了darvadstrocel在扩大患者群体中的疗效和安全性。

Methods

ADMIRE CD II (ClinicalTrials.gov, Number: NCT03279081) was a phase 3, double-blind, randomized, placebo-controlledtrial conducted in Europe, Israel, and North America.

ADMIRE CD II (ClinicalTrials.gov, 编号: NCT03279081) 是一项在欧洲、以色列和北美进行的3期、双盲、随机、安慰剂对照试验。

Adults with Crohn's disease and complex perianal fistulas with ≤2 internal openings and ≤3 external openings and inadequate response to immunosuppressive agents or biologics were randomized 1:1 to receive darvadstrocel (a dispersion of 120 × 106 stem cells in 24 mL sterile buffered solution) or placebo.

患有克罗恩病和复杂肛周瘘管的成人，瘘管内口≤2个，外口≤3个，并且对免疫抑制剂或生物制剂反应不足，被随机1:1分配接受darvadstrocel（120×10^6干细胞分散在24毫升无菌缓冲溶液中）或安慰剂治疗。

Both groups underwent curettage and closure of the internal opening.

两组患者均接受了搔刮术和内口闭合术。

The primary endpoint was combined remission (closure of all treated external openings and absence of collections >2 cm) at week 24.

主要终点是第24周时的综合缓解（所有治疗的外部开口闭合且无大于2厘米的积液）。

Results

Overall, 568 patients were randomized to receive darvadstrocel (n = 283) or placebo (n = 285); 249 and 246, respectively, completed the trial. At week 24, combined remission was achieved in 138 of 283 (48.8%) patients in the darvadstrocel group and 132 of 285 (46.3%) in the placebo group (estimated treatment difference: 2.4%; 95% CI, -5.8 to 10.6; P = .571).

总体而言，共有568名患者被随机分配接受darvadstrocel治疗（n = 283）或安慰剂（n = 285）；分别有249名和246名患者完成了试验。在第24周时，darvadstrocel组的283名患者中有138名（48.8%）和安慰剂组的285名患者中有132名（46.3%）实现了联合缓解（估计治疗差异：2.4%；95%置信区间，-5.8至10.6；P = .571）。

There were no significant differences in key secondary endpoints for darvadstrocel vs placebo (clinical remission at week 24 [P = .515] and time to clinical remission [P = .374]).

在darvadstrocel与安慰剂的关键次要终点方面没有显著差异（第24周的临床缓解[P = .515]和临床缓解时间[P = .374]）。

Treatment-emergent adverse events were infrequent and experienced by similar proportions of patients receiving darvadstrocel (203/278 [73.0%]) and placebo (201/274 [73.4%]).

治疗相关不良事件发生率较低，接受darvadstrocel治疗的患者（278名中有203名，占73.0%）和接受安慰剂治疗的患者（274名中有201名，占73.4%）中出现不良事件的比例相似。

Conclusions

ADMIRE CD II did not meet its primary endpoint of combined remission at week 24, with no statistically significant difference between darvadstrocel and placebo.

ADMIRE CD II研究未达到其主要终点，即第24周的联合缓解率，darvadstrocel与安慰剂之间没有统计学显著差异。

No new safety signals were identified for darvadstrocel.

未发现达伐斯特罗塞尔的新安全信号。

clinicaltrials

gov, Number: NCT002209456.

政府注册号：NCT002209456。