Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial.

The authors conducted a trial to establish the efficacy and safety of glepaglutide in reducing parenteral support (PS) needs in patients with SBS with intestinal failure.

作者进行了一项试验，以确定glepaglutide在减少短肠综合征（SBS）伴肠衰竭患者肠外支持（PS）需求方面的有效性和安全性。

Methods

In an international, placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, patients with SBS with intestinal failure requiring PS ≥3 d/wk were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice weekly or once weekly or placebo.

在一项国际、安慰剂对照、随机、平行组、双盲、III期试验中，需要每周PS≥3天的SBS肠道衰竭患者按1:1:1的比例随机分配接受24周的glepaglutide 10 mg每周两次或每周一次或安慰剂治疗。

PS volume was equivalently reduced if mean urine volume of a 48-hour balance period exceeded baseline values by >10%.

如果48小时平衡期的平均尿量比基线值高出>10%，则PS体积等效减少。

Results

One hundred six patients were randomized and dosed.

106名患者被随机分组并接受了剂量分配。

Glepaglutide twice weekly significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, -5.13 vs -2.85 L/wk; P = .0039; primary end point).

与安慰剂相比，每周两次的Glepaglutide显著降低了从基线到第24周的每周PS体积（平均变化，-5.13对比-2.85 L/周；P = .0039；主要终点）。

Results were similar across major anatomic subgroups.

主要解剖亚组的结果相似。

Glepaglutide twice weekly was also superior to placebo for key secondary end points of proportion of patients achieving clinical response, defined as ≥20% PS volume reduction from baseline to weeks 20 and 24 (65.7% vs 38.9%; P = .0243) and patients achieving a reduction in days on PS ≥1 d/wk from baseline to week 24 (51.4% vs 19.4%; P = .0043).

Glepaglutide每周两次在主要次要终点方面也优于安慰剂，这些终点定义为从基线到第20周和第24周实现临床反应的患者比例，即PS体积减少≥20%（65.7%对比38.9%；P = .0243），以及从基线到第24周实现PS天数每周减少≥1天的患者比例（51.4%对比19.4%；P = .0043）。

Complete PS weaning ("enteral autonomy") was achieved for 5 patients (14%) receiving glepaglutide twice weekly vs 0 for patients receiving placebo.

5名（14%）接受每周两次glepaglutide治疗的患者实现了完全的PS（经口营养）独立（"肠内自主"），而接受安慰剂的患者中没有实现。

No statistically significant differences were found for glepaglutide once weekly vs placebo for primary or key secondary end points.

对于glepaglutide每周一次与安慰剂相比，在主要或关键次要终点上没有发现统计学上的显著差异。

Significant glepaglutide benefits on patient-reported outcome (Patient Global Impression of Change) were found.

发现glepaglutide对患者报告的结果（患者整体变化印象）有显著益处。

Glepaglutide was assessed to be safe and well tolerated.

评估认为glepaglutide安全且耐受性良好。

Conclusions

Glepaglutide treatment in patients with SBS with intestinal failure resulted in clinically relevant reductions in PS requirements and was well tolerated.

Glepaglutide治疗在短肠综合征伴有肠衰竭的患者中，导致了对肠外营养需求的临床相关减少，并且耐受性良好。

(ClinicalTrials.gov, Number: NCT03690206; ClinicalTrialsRegister.eu, Number: 2017-004394-14.).

(ClinicalTrials.gov, 编号: NCT03690206; ClinicalTrialsRegister.eu, 编号: 2017-004394-14.)