吸入用伊曲康唑治疗哮喘合并变应性支气管肺曲霉病成人患者的安全性与有效性（PUR1900-ABPA研究）：一项随机、双盲、
2026/07/31
摘要
背景：变应性支气管肺曲霉病（ABPA）目前尚无获批疗法，全球约480万哮喘患者受其影响。当前采用的口服糖皮质激素或口服伊曲康唑治疗，受限于全身毒性、药物间相互作用及气道局部药物浓度欠佳等问题。PUR1900是一种新型吸入用伊曲康唑制剂，旨在实现气道高浓度给药，同时最大限度减少全身暴露。
方法： 本项为2期、多中心、随机、双盲、平行分组、安慰剂对照试验。纳入哮喘合并ABPA的成人受试者，按2：2：1比例随机分配至吸入PUR1900 20 mg组、PUR1900 40 mg组或安慰剂组，每日一次，持续16周。关键入组标准包括：血清总IgE≥1000 kU·L⁻¹、哮喘控制问卷（ACQ）-7评分 >1.5、支气管扩张剂使用前第一秒用力呼气容积（FEV₁）为预计值的50%–85%。本研究未预设主要终点，评估了肺功能、免疫学及患者报告结局等多个探索性指标。
结果：共随机入组43例受试者（20 mg组，n=18；40 mg组，n=16；安慰剂组，n=9）；39例完成治疗。基线特征均衡。第16周时，PUR1900 40 mg组较安慰剂组在FEV₁（最小二乘均数[LSM] +0.28 L；95%置信区间[CI]：0.02，0.53）和ACQ-7（LSM -0.51分；95% CI：-0.97，-0.06）方面均有改善，血清总IgE水平降低（LSM -2619 kU·L⁻¹；95% CI：-5342，105）。PUR1900 20 mg组未观察到较安慰剂组的改善效应。不良事件发生率在40 mg组、20 mg组和安慰剂组分别为31%、39%和44%，均无严重不良事件。
结论：PUR1900 40 mg剂量在ABPA关键临床领域表现出改善作用，且安全性良好，支持进一步开展3期临床试验评估。
Safety and efficacy of inhaled itraconazole in adults with asthma and allergic bronchopulmonary aspergillosis (PUR1900-ABPA): a randomized, double-blind, parallel group, placebo-controlled, multicenter, phase 2 trial.
Ritesh, Agarwal; Dhruv
Abstrast
BACKGROUND: No therapies are approved for allergic bronchopulmonary aspergillosis (ABPA), which affects an estimated 4.8 million asthmatic individuals worldwide. Current treatment with oral corticosteroids or oral itraconazole is limited by systemic toxicities, drug-drug interactions, and suboptimal airway drug concentrations. PUR1900 is a novel inhaled itraconazole formulation designed to achieve high airway concentrations with minimal systemic exposure.
METHODS: We conducted a phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Adults with asthma and ABPA were randomized (2:2:1) to receive inhaled PUR1900 20 mg, PUR1900 40 mg, or placebo once daily for 16 weeks. Key eligibility criteria included serum total IgE ≥1000 kU·L(-1), Asthma Control Questionnaire (ACQ)-7 score >1.5, and pre-bronchodilator FEV(1) 50-85% predicted. The study had no prespecified primary endpoint and evaluated multiple exploratory outcomes across lung function, immunological, and patient-reported domains.
RESULTS: We randomized 43 participants (20 mg, n=18; 40 mg, n=16; placebo, n=9); 39 completed treatment. Baseline characteristics were balanced. At week 16, PUR1900 40 mg was associated with placebo-adjusted improvements in FEV(1) (LSM +0.28 L; 95% CI: 0.02, 0.53) and ACQ-7 (LSM -0.51 points; 95% CI: -0.97, -0.06), with reductions in serum total IgE (LSM -2619 kU·L(-1); 95% CI: -5342, 105). No placebo-adjusted effects were observed with PUR1900 20 mg. Adverse events occurred in 31%, 39%, and 44% of participants receiving 40 mg, 20 mg, and placebo, respectively; none were serious.
CONCLUSIONS: PUR1900 40 mg was associated with improvements across key clinical domains in ABPA, with a favorable safety profile, supporting further phase 3 evaluation.
背景：变应性支气管肺曲霉病（ABPA）目前尚无获批疗法，全球约480万哮喘患者受其影响。当前采用的口服糖皮质激素或口服伊曲康唑治疗，受限于全身毒性、药物间相互作用及气道局部药物浓度欠佳等问题。PUR1900是一种新型吸入用伊曲康唑制剂，旨在实现气道高浓度给药，同时最大限度减少全身暴露。
方法： 本项为2期、多中心、随机、双盲、平行分组、安慰剂对照试验。纳入哮喘合并ABPA的成人受试者，按2：2：1比例随机分配至吸入PUR1900 20 mg组、PUR1900 40 mg组或安慰剂组，每日一次，持续16周。关键入组标准包括：血清总IgE≥1000 kU·L⁻¹、哮喘控制问卷（ACQ）-7评分 >1.5、支气管扩张剂使用前第一秒用力呼气容积（FEV₁）为预计值的50%–85%。本研究未预设主要终点，评估了肺功能、免疫学及患者报告结局等多个探索性指标。
结果：共随机入组43例受试者（20 mg组，n=18；40 mg组，n=16；安慰剂组，n=9）；39例完成治疗。基线特征均衡。第16周时，PUR1900 40 mg组较安慰剂组在FEV₁（最小二乘均数[LSM] +0.28 L；95%置信区间[CI]：0.02，0.53）和ACQ-7（LSM -0.51分；95% CI：-0.97，-0.06）方面均有改善，血清总IgE水平降低（LSM -2619 kU·L⁻¹；95% CI：-5342，105）。PUR1900 20 mg组未观察到较安慰剂组的改善效应。不良事件发生率在40 mg组、20 mg组和安慰剂组分别为31%、39%和44%，均无严重不良事件。
结论：PUR1900 40 mg剂量在ABPA关键临床领域表现出改善作用，且安全性良好，支持进一步开展3期临床试验评估。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Eur Respir J 2026 Jul 16;(0);11(1).DOI:10.1183/13993003.00058-2026. IF: 12.339）
（Eur Respir J 2026 Jul 16;(0);11(1).DOI:10.1183/13993003.00058-2026. IF: 12.339）
Safety and efficacy of inhaled itraconazole in adults with asthma and allergic bronchopulmonary aspergillosis (PUR1900-ABPA): a randomized, double-blind, parallel group, placebo-controlled, multicenter, phase 2 trial.
Ritesh, Agarwal; Dhruv
Abstrast
BACKGROUND: No therapies are approved for allergic bronchopulmonary aspergillosis (ABPA), which affects an estimated 4.8 million asthmatic individuals worldwide. Current treatment with oral corticosteroids or oral itraconazole is limited by systemic toxicities, drug-drug interactions, and suboptimal airway drug concentrations. PUR1900 is a novel inhaled itraconazole formulation designed to achieve high airway concentrations with minimal systemic exposure.
METHODS: We conducted a phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Adults with asthma and ABPA were randomized (2:2:1) to receive inhaled PUR1900 20 mg, PUR1900 40 mg, or placebo once daily for 16 weeks. Key eligibility criteria included serum total IgE ≥1000 kU·L(-1), Asthma Control Questionnaire (ACQ)-7 score >1.5, and pre-bronchodilator FEV(1) 50-85% predicted. The study had no prespecified primary endpoint and evaluated multiple exploratory outcomes across lung function, immunological, and patient-reported domains.
RESULTS: We randomized 43 participants (20 mg, n=18; 40 mg, n=16; placebo, n=9); 39 completed treatment. Baseline characteristics were balanced. At week 16, PUR1900 40 mg was associated with placebo-adjusted improvements in FEV(1) (LSM +0.28 L; 95% CI: 0.02, 0.53) and ACQ-7 (LSM -0.51 points; 95% CI: -0.97, -0.06), with reductions in serum total IgE (LSM -2619 kU·L(-1); 95% CI: -5342, 105). No placebo-adjusted effects were observed with PUR1900 20 mg. Adverse events occurred in 31%, 39%, and 44% of participants receiving 40 mg, 20 mg, and placebo, respectively; none were serious.
CONCLUSIONS: PUR1900 40 mg was associated with improvements across key clinical domains in ABPA, with a favorable safety profile, supporting further phase 3 evaluation.
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