Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: a multicenter, randomized, double-blind, phase 3A clinical trial (NIMBLE).

Background

Investigate the efficacy and safety of switching to depemokimab in participants with severe asthma already managed with and responsive to short-acting biologic therapies targeting IL-5 or its receptor.

研究在已经使用并针对 IL-5 或其受体的短效生物制剂治疗且有反应的重度哮喘患者中，转换为使用 depemokimab 的疗效和安全性。

Methods

NIMBLE (NCT04718389) was a multicenter, randomized, double-blind, double-dummy, parallel-group, phase 3A noninferiority study.

NIMBLE (NCT04718389) 是一项多中心、随机、双盲、双模拟、平行组、3A 期非劣效性研究。

Participants were ≥12 years old with asthma and documented clinical benefit on mepolizumab 100 mg subcutaneously every 4 weeks or benralizumab 30 mg subcutaneously every 8 weeks for ≥12 months.

参与者年龄≥12岁，患有哮喘，并且在每4周皮下注射100毫克美泊利单抗或每8周皮下注射30毫克贝拉利单抗≥12个月后，有明确的临床获益。

Participants were randomized 1:1 to depemokimab 100 mg subcutaneously every 26 weeks or maintained on their prior biologic (mepolizumab or benralizumab).

参与者按1:1的比例随机分配接受每26周皮下注射100 mg的depemokimab或继续使用他们之前的生物制剂（mepolizumab或benralizumab）。

The primary endpoint was annualized rate of clinically significant exacerbations over 52 weeks, with predefined noninferiority margin set at 1.28.

主要终点是52周内临床显著加重的年化率，预设的非劣效性边界设定为1.28。

Safety endpoints included adverse events.

安全性终点包括不良事件。

measurements_and_main_results

Annualized rates (95% confidence intervals [CIs]) of clinically significant exacerbations over 52 weeks were 0.57 (0.50 to 0.64) with depemokimab (n = 848) and 0.49 (0.43 to 0.55) with active comparator (n = 839); the rate ratio (95% CI) was 1.16 (0.98 to 1.38).

52周内临床显著恶化的年化率（95%置信区间[CI]）为：depemokimab组（n = 848）为0.57（0.50至0.64），活性对照组（n = 839）为0.49（0.43至0.55）；比率比（95% CI）为1.16（0.98至1.38）。

Since the upper bound of the 95% CI exceeded 1.28, noninferiority was not met.

由于95%置信区间的上限超过了1.28，因此未满足非劣效性。

Most participants in both treatment arms experienced no clinically significant exacerbations.

在两个治疗组中，大多数参与者没有经历任何临床上显著的加重。

Health-related quality of life, asthma control, and lung function outcomes were stable throughout the study.

在整个研究期间，健康相关的生活质量、哮喘控制和肺功能结果保持稳定。

Adverse events were comparable between treatment groups.

治疗组之间的不良事件相当。

Conclusions

While statistical noninferiority was not met, exacerbation rates were low and symptom control/lung function were maintained in both groups.

尽管未达到统计学上的非劣效性，但两组的急性加重率都较低，症状控制和肺功能得到了维持。

This first randomized, controlled switch trial in severe asthma suggests that participants with severe asthma on mepolizumab or benralizumab may safely switch to twice-yearly depemokimab.

这项针对重度哮喘患者的首次随机对照转换试验表明，正在接受美泊利单抗或贝拉利单抗治疗的重度哮喘患者可以安全地转换为每半年使用一次的depemokimab治疗。