Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial.

We aimed to assess the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A monoclonal antibody, in adults with moderately to severely active Crohn's disease.

我们的目标是评估抗TNF样细胞因子1A单克隆抗体duvakitug在中度至重度活动性克罗恩病成人患者中的疗效和安全性。

Methods

In this multicentre, placebo-controlled, phase 2b study, we enrolled adults (aged 18-75 years) with moderately to severely active Crohn's disease (including inadequate response, loss of response, or intolerance to previous therapies).

在这项多中心、安慰剂对照的2b期研究中，我们招募了18-75岁的成年患者，这些患者患有中度至重度活动性克罗恩病（包括对先前治疗反应不足、反应丧失或不耐受）。

We randomly assigned (1:1:1) participants to receive 2250 mg duvakitug loading dose subcutaneously, followed by duvakitug 450 mg or 900 mg every 2 weeks, or placebo loading dose, then placebo every 2 weeks.

我们按1:1:1的比例随机分配参与者，接受2250毫克duvakitug负荷剂量皮下注射，随后每两周接受450毫克或900毫克duvakitug，或接受安慰剂负荷剂量，然后每两周接受安慰剂。

The primary endpoint, endoscopic response (≥50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease) at week 14, was analysed using Bayesian methodology.

主要终点为第14周时内镜反应（从基线起对克罗恩病简单内镜评分减少≥50%），采用贝叶斯方法进行分析。

A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was at least 0·90.

如果后验概率至少为0·90，表明duvakitug剂量的反应率超过安慰剂，则该剂量被宣布为成功。

Analyses were done in the modified intention-to-treatpopulation, which included all patients who received at least one dose of their assigned treatment.

分析是在改良意向治疗人群中进行的，该人群包括所有至少接受了一次指定治疗的患者。

This trial was registered with ClinicalTrials.gov, NCT05499130, and has been completed.

这项试验已在ClinicalTrials.gov上注册，注册号为NCT05499130，并已完成。

Results

Patients were enrolled from Sept 30, 2022, to Nov 12, 2024.

患者从2022年9月30日开始入组，至2024年11月12日结束。

We screened 275 patients with Crohn's disease, of whom 139 (51%) patients were randomly assigned to receive either duvakitug 450 mg (n=46), duvakitug 900 mg (n=47), or placebo (n=46).

我们筛查了275名克罗恩病患者，其中139名（51%）患者被随机分配接受450毫克的duvakitug（n=46），900毫克的duvakitug（n=47）或安慰剂（n=46）。

One patient in the duvakitug 900 mg did not receive study drug; the modified intention-to-treatpopulation therefore included 46 patients in the 450 mg group, 46 in the 900 mg group, and 46 in the placebo group. 78 (57%) patients were previously exposed to at least one advanced therapy.

一名患者在duvakitug 900 mg组未接受研究药物；因此，修改后的意向治疗人群包括450 mg组的46名患者，900 mg组的46名患者和安慰剂组的46名患者。78名（57%）患者之前至少接受过一种先进治疗。

The mean age of enrolled patients was 39·5 years (SD 14·7); 58 (42%) were female, 80 (58%) were male, and 131 (95%) were White. 12 (26%) of 46 patients in the duvakitug 450 mg group, 22 (48%) of 46 in the duvakitug 900 mg group, and six (13%) of 46 in the placebo group had an endoscopic response at week 14.

入组患者的平均年龄为39.5岁（标准差14.7）；58名（42%）为女性，80名（58%）为男性，131名（95%）为白人。在第14周，450 mg组的46名患者中有12名（26%），900 mg组的46名患者中有22名（48%），安慰剂组的46名患者中有6名（13%）出现了内镜反应。

The difference in posterior mean response rates versus placebo was 13% (95% credible interval -3 to 29) for duvakitug 450 mg and 33% (16 to 50) for duvakitug 900 mg, with posterior probabilities of superiority of 0·94 for duvakitug 450 mg and greater than 0·99 for duvakitug 900 mg.

与安慰剂相比，duvakitug 450 mg的后验平均反应率差异为13%（95%可信区间-3至29），duvakitug 900 mg的差异为33%（16至50），duvakitug 450 mg的优越性后验概率为0.94，duvakitug 900 mg的优越性后验概率大于0.99。

Adverse events occurred in 31 (67%) of 46 patients in the duvakitug 450 mg group, 20 (43%) of 46 in the duvakitug 900 mg group, and 22 (48%) of 46 in the placebo group.

在duvakitug 450 mg组的46名患者中，有31名（67%）发生了不良事件，在duvakitug 900 mg组的46名患者中，有20名（43%）发生了不良事件，在安慰剂组的46名患者中，有22名（48%）发生了不良事件。

The most frequent adverse events were nasopharyngitis (two in the 450 mg group, three in the 900 mg group, and three in the placebo group) and headache (four in the 450 mg group, one in the 900 mg group, and one in the placebo group).

最常见的不良事件是鼻咽炎（450 mg组2例，900 mg组3例，安慰剂组3例）和头痛（450 mg组4例，900 mg组1例，安慰剂组1例）

Serious adverse events occurred in six (13%) patients in the duvakitug 450 mg group, one (2%) in the duvakitug 900 mg group, and five (11%) in the placebo group.

严重不良事件发生在duvakitug 450 mg组的六名（13%）患者中，duvakitug 900 mg组的一名（2%）患者中，以及安慰剂组的五名（11%）患者中。

interpretation

Duvakitug showed significant evidence for endoscopic response versus placebo in patients with moderately to severely active Crohn's disease, with no safety concerns identified.

Duvakitug 在中度至重度活动性克罗恩病患者中显示出与安慰剂相比显著的内镜反应证据，未发现安全问题。

funding

Teva and Sanofi.

Teva 和 Sanofi。