Efficacy and safety of the CD40 ligand inhibitor dapirolizumab pegol in systemic lupus erythematosus (PHOENYCS GO): a randomised, double-blind, placebo-controlled, phase 3 trial.

In this phase 3 trial, we aimed to evaluate the efficacy and safety of dapirolizumab pegol in patients with systemic lupus erythematosus (SLE).

在这项 III 期试验中，我们旨在评估 dapirolizumab pegol 在系统性红斑狼疮（SLE）患者中的疗效和安全性。

Methods

PHOENYCS GO was a 48-week, randomised, double-blind, placebo-controlled, phase 3 trial conducted in 177 centres (hospitals, private practices, and trial centres) in 25 countries.

PHOENYCS GO 是一项为期48周、随机、双盲、安慰剂对照的3期临床试验，在25个国家的177个中心（医院、私人诊所和试验中心）进行。

Patients aged 16 years or older with moderate-to-severe, active SLE despite standard-of-care medication were randomly assigned (2:1), via an interactive web response system, to intravenous dapirolizumab pegol 24 mg/kg or placebo every 4 weeks in addition to standard of care.

年龄在16岁或以上的中度至重度活动性系统性红斑狼疮（SLE）患者，尽管接受了标准治疗，仍被随机分配（2:1），通过交互式网络响应系统，每4周接受一次静脉注射达比加群聚乙二醇24 mg/kg或安慰剂，同时继续接受标准治疗。

Patients, investigators, and funders were blinded to treatment assignments.

患者、研究者和资助者对治疗分配情况均不知情。

The primary outcome was British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 48.

主要研究结果是第48周基于英国群岛狼疮评估小组的综合狼疮评估（BICLA）反应。

Efficacy analyses were conducted on a modified intention-to-treatpopulation.

疗效分析是在修改后的意向治疗人群中进行的。

Safety analyses included all randomly assigned patients who received at least one study medication dose.

安全性分析包括所有随机分配并至少接受一次研究药物剂量的患者。

This trial is registered with ClinicalTrials.gov (NCT04294667) and is completed.

该试验已在ClinicalTrials.gov注册（NCT04294667），并已完成。

Results

Between Aug 12, 2020, and June 8, 2023, 643 patients were screened and 321 patients were randomly assigned to dapirolizumab pegol (n=213) or placebo (n=108) plus standard of care.

在2020年8月12日至2023年6月8日期间，共有643名患者接受了筛查，其中321名患者被随机分配接受达皮罗利单抗聚乙二醇（n=213）或安慰剂（n=108）加标准治疗。

All randomly assigned patients received at least one dose of study medication.

所有随机分配的患者至少接受了研究药物的一剂治疗。

Six patients were excluded due to non-compliance of one site with Good Clinical Practice guidelines; therefore, the full-analysis set included 315 patients (293 female, 22 male).

由于一个研究地点未遵守良好临床实践指南，六名患者被排除在外；因此，全分析集包括315名患者（293名女性，22名男性）。

A significantly greater proportion of patients receiving dapirolizumab pegol (50% [103/208]) versus placebo (35% [37/107]) had BICLA response at week 48 (p=0·011; difference 14·6; 95% CI 3·3-25·8).

在第48周时，接受达匹罗珠单抗佩戈尔治疗的患者中有50%（103/208）达到了BICLA反应，而接受安慰剂治疗的患者中这一比例为35%（37/107），差异具有统计学意义（p=0·011；差异值14·6；95%置信区间3·3-25·8）。

Treatment-emergent adverse events occurred in 83% (176/213) of patients receiving dapirolizumab pegol versus 75% (81/108) receiving placebo.

接受达匹罗珠单抗佩戈尔治疗的患者中有83%（176/213）出现了治疗后不良事件，而接受安慰剂治疗的患者中这一比例为75%（81/108）。

Serious treatment-emergent adverse events occurred in 10% (21/213) of patients receiving dapirolizumab pegol versus 15% (16/108) receiving placebo.

在接受达匹罗珠单抗聚乙二醇治疗的患者中，有10%（21/213）出现了严重的治疗后不良事件，而在接受安慰剂治疗的患者中，这一比例为15%（16/108）。

Hypersensitivity reactions during infusion occurred in 3% (6/213) of patients receiving dapirolizumab pegol.

在接受达匹罗珠单抗聚乙二醇治疗的患者中，有3%（6/213）在输液过程中出现了超敏反应。

Serious infections occurred in 4% (8/213) and 6% (6/108) of patients receiving dapirolizumab pegol and placebo, respectively.

分别有4%（8/213）和6%（6/108）的患者在接受达匹罗珠单抗聚乙二醇和安慰剂治疗时发生了严重感染。

One thromboembolic event (myocardial infarction) occurred in one patient in the dapirolizumab pegol group and one death (gangrene-related sepsis) occurred in another patient in the dapirolizumab pegol group.

在达匹罗珠单抗聚乙二醇组中，有一名患者发生了血栓栓塞事件（心肌梗死），另一名患者发生了与坏疽相关的败血症死亡。

interpretation

Dapirolizumab pegol was associated with significant improvement in disease activity in patients with SLE.

达皮罗利珠单抗聚乙二醇与系统性红斑狼疮患者疾病活动度显著改善相关。

These findings support the further investigation of dapirolizumab pegol as a treatment option for SLE.

这些发现支持进一步研究达皮罗利珠单抗聚乙二醇作为系统性红斑狼疮治疗选择的必要性。

funding

UCB and Biogen.

UCB和Biogen。