Rademikibart Treatment for Moderate-to-Severe Uncontrolled Asthma: A Phase 2B Randomized Clinical Trial.

Objectives: We sought to evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma.

目标：我们旨在评估Rademikibart在中度至重度持续性未控制哮喘成年患者中的疗效。

Methods: In this global Phase 2b trial, 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, after a 600-mg loading dose) or a placebo group; rademikibart or placebo was administered subcutaneously for 24 weeks.

方法：在这项全球2b期试验中，322名患者被随机分为1:1:1的三组，分别接受两种剂量的rademikibart治疗（150 mg或300 mg，每两周一次，经过600-mg的负荷剂量）或安慰剂组；rademikibart或安慰剂通过皮下注射给药，持续24周。

Measurements and Main Results: Prebronchodilator (trough) forced expiratory volume in 1 second (FEV1) at Week 12 (primary endpoint) improved with rademikibart at 150 mg and 300 mg: Least squares mean changes (95% confidence interval), above placebo, were 140 ml (44-236 ml; P = 0.005) and 189 ml (92-286 ml; P < 0.001), respectively.

测量和主要结果：在第12周时，使用支气管扩张剂前（谷值）的第一秒钟用力呼气量（FEV1）（主要终点）随着150 mg和300 mg的rademikibart治疗而改善：最小二乘均值变化（95%置信区间），高于安慰剂，分别为140毫升（44-236毫升；P = 0.005）和189毫升（92-286毫升；P < 0.001）。

Prebronchodilator (trough) FEV1 improvements occurred rapidly during Week 1, were sustained through Week 24, and were greatest in patients with high baseline blood eosinophils (patients with ⩾300 eosinophils/ml experienced placebo-adjusted FEV1 improvement at Week 24 of 420 ml [95% confidence interval= 239-600 ml] in the 300-mg group).

在第1周内，使用支气管扩张剂前（谷值）FEV1的改善迅速发生，并持续至第24周，且在基线时血液嗜酸性粒细胞水平较高的患者中最为显著（血液嗜酸性粒细胞水平⩾300个/ml的患者在第24周时，300mg组的安慰剂校正FEV1改善为420毫升[95%置信区间=239-600毫升]）。

Rapid and sustained statistically significant improvements were also observed in percent predicted FEV1 and Asthma Control Questionnaire score across 24 weeks.

在24周内，预测FEV1百分比和哮喘控制问卷评分也观察到快速且持续的统计学显著改善。

Through Week 24, proportions of patients with one or more exacerbations were 7.5% (150 mg) and 9.3% (300 mg) versus 16.7% (placebo).

截至第24周，出现一次或多次加重的患者比例分别为150毫克组的7.5%和300毫克组的9.3%，而安慰剂组为16.7%。

Eighty-eight percent of patients completed treatment.

88%的患者完成了治疗。

Treatment-emergent adverse events were generally similar to placebo, and no eosinophilia was observed.

治疗后出现的不良事件总体上与安慰剂相似，未观察到嗜酸性粒细胞增多。

Injection site reactions were mostly mild.

注射部位的反应大多为轻度。

The most common treatment-emergent adverse events (10-12% of patients) were cough, coronavirus disease (COVID-19), and dyspnea.

最常见的治疗后不良事件（占患者10-12%）是咳嗽、冠状病毒病（COVID-19）和呼吸困难。

Conclusions: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy.

结论：在24周的拉德米基巴特治疗期间，肺功能和哮喘控制得到了快速且持续的改善。

Clinical trial registered with www.clinicaltrials.gov (NCT04773678).

临床试验已在www.clinicaltrials.gov注册（NCT04773678）。