Rademikibart治疗中重度、未控制哮喘：一项2B期随机试验
2025/04/06
摘要
背景：Rademikibart（前身为CBP-201）是一种针对IL-4Rα的抗体。
目的：本研究旨在评估rademikibart在患有中重度、持续性、未控制的哮喘成年人中的疗效。
方法：本研究为一项全球2b期试验（NCT04773678），322名患者以1:1:1的比例随机分为两组，分别为rademikibart组（每两周150 mg或300 mg，负荷剂量为600 mg）或安慰剂组，皮下注射24周。
结果：在第12周（主要终点），使用150 mg和300 mg的rademikibart后，支气管扩张剂前第1秒的用力呼气量（FEV1）（谷值）有所改善：与安慰剂相比，最小二乘平均变化（95%CI）分别为+140 mL（+44~236 mL；p=0.005）和+189 mL（+92~286 mL；p<0.001）。支气管扩张剂前FEV1谷值改善在第1周迅速发生，持续到第24周，在基线外周血嗜酸性粒细胞水平较高的患者中改善最明显（300mg治疗组中嗜酸性粒细胞数≥300/mL的患者在第24周接受安慰剂校正后的FEV1改善值为+420mL[95%CI，+239～600mL]）。在24周内，FEV1占预计值的百分比和哮喘控制问卷得分也得到快速、持续地改善，且存在统计学意义。在第24周，急性发作≥1次的患者比例分别为7.5%（150mg治疗组）和9.3%（300mg治疗组），而安慰剂组为16.7%。88%的患者接受了完整治疗。治疗中出现的不良事件（TEAE）通常与安慰剂相似，没有观察到嗜酸性粒细胞增多。注射部位反应大多较轻。最常见的TEAE（10%～12%）为咳嗽、新冠肺炎和呼吸困难。
结论：经过24周rademikibart治疗，受试者的肺功能和哮喘控制得到快速、持续地改善。
Rademikibart Treatment for Moderate-to-Severe, Uncontrolled Asthma: A Phase 2B Randomized Trial.
Kerwin E, Yang T, Su N, Guo J, Adivikolanu R, Longphre M, Wang J, Yun J, Pan W, Wei Z, Collazo R.
Abstract
BACKGROUND:Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody.
OBJECTIVES:To evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma.
METHODS:In this global phase 2b trial (NCT04773678), 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, following a 600 mg loading dose) or placebo, administered subcutaneously, for 24 weeks.
RESULTS:Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV1) at Week 12 (primary endpoint) improved with rademikibart 150 mg and 300 mg: least squares mean changes (95% CI), above placebo, were +140 mL (+44-236 mL; p=0.005) and +189 mL (+92-286 mL; p<0.001), respectively. Prebronchodilator trough FEV1 improvements occurred rapidly during Week 1, were sustained through Week 24, and 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% CI, +239-600 mL] in the 300 mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV1 and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with ≥1 exacerbation were 7.5% (150 mg) and 9.3% (300 mg) vs 16.7% (placebo). 88% of patients completed treatment. Treatment-emergent adverse events (TEAEs) were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common TEAEs (10%～12% of patients) were cough, COVID-19, and dyspnea.
CONCLUSION: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy.
背景：Rademikibart（前身为CBP-201）是一种针对IL-4Rα的抗体。
目的：本研究旨在评估rademikibart在患有中重度、持续性、未控制的哮喘成年人中的疗效。
方法：本研究为一项全球2b期试验（NCT04773678），322名患者以1:1:1的比例随机分为两组，分别为rademikibart组（每两周150 mg或300 mg，负荷剂量为600 mg）或安慰剂组，皮下注射24周。
结果：在第12周（主要终点），使用150 mg和300 mg的rademikibart后，支气管扩张剂前第1秒的用力呼气量（FEV1）（谷值）有所改善：与安慰剂相比，最小二乘平均变化（95%CI）分别为+140 mL（+44~236 mL；p=0.005）和+189 mL（+92~286 mL；p<0.001）。支气管扩张剂前FEV1谷值改善在第1周迅速发生，持续到第24周，在基线外周血嗜酸性粒细胞水平较高的患者中改善最明显（300mg治疗组中嗜酸性粒细胞数≥300/mL的患者在第24周接受安慰剂校正后的FEV1改善值为+420mL[95%CI，+239～600mL]）。在24周内，FEV1占预计值的百分比和哮喘控制问卷得分也得到快速、持续地改善，且存在统计学意义。在第24周，急性发作≥1次的患者比例分别为7.5%（150mg治疗组）和9.3%（300mg治疗组），而安慰剂组为16.7%。88%的患者接受了完整治疗。治疗中出现的不良事件（TEAE）通常与安慰剂相似，没有观察到嗜酸性粒细胞增多。注射部位反应大多较轻。最常见的TEAE（10%～12%）为咳嗽、新冠肺炎和呼吸困难。
结论：经过24周rademikibart治疗，受试者的肺功能和哮喘控制得到快速、持续地改善。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Am J Respir Crit Care Med. 2025 Feb 25. doi: 10.1164/rccm.202409-1708OC.）
Rademikibart Treatment for Moderate-to-Severe, Uncontrolled Asthma: A Phase 2B Randomized Trial.
Kerwin E, Yang T, Su N, Guo J, Adivikolanu R, Longphre M, Wang J, Yun J, Pan W, Wei Z, Collazo R.
Abstract
BACKGROUND:Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody.
OBJECTIVES:To evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma.
METHODS:In this global phase 2b trial (NCT04773678), 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, following a 600 mg loading dose) or placebo, administered subcutaneously, for 24 weeks.
RESULTS:Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV1) at Week 12 (primary endpoint) improved with rademikibart 150 mg and 300 mg: least squares mean changes (95% CI), above placebo, were +140 mL (+44-236 mL; p=0.005) and +189 mL (+92-286 mL; p<0.001), respectively. Prebronchodilator trough FEV1 improvements occurred rapidly during Week 1, were sustained through Week 24, and 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% CI, +239-600 mL] in the 300 mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV1 and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with ≥1 exacerbation were 7.5% (150 mg) and 9.3% (300 mg) vs 16.7% (placebo). 88% of patients completed treatment. Treatment-emergent adverse events (TEAEs) were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common TEAEs (10%～12% of patients) were cough, COVID-19, and dyspnea.
CONCLUSION: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy.
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