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.

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 FEV1 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 FEV1 (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.