Efficacy and safety of GSK3772847 in participants with moderate-to-severe asthma with allergic fungal airway disease: A phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial

Abstract

Introduction Current treatments for allergic fungal airway disease are not specific for asthma and are associated with limited efficacy or safety concerns. This Phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial assessed the efficacy and safety of GSK3772847, an anti-interleukin-33 receptor monoclonal antibody, in moderate-to-severe asthma patients with allergic fungal airway disease (ClinicalTrials.gov: NCT03393806). Methods Key inclusion criteria required participants of ≥18 years of age with a documented diagnosis of moderate-to-severe asthma (≥12 months) treated with inhaled corticosteroid and long-acting β2-agonist (≥4 months); evidence of allergic fungal airway disease (fungal sensitization to Aspergillus fumigatus [>0.35 KU/L] or Penicillium chrysogenum [>0.35 KU/L] and no history of concurrent respiratory disease/recurrent or ongoing non-pulmonary infections. Participants were randomized (1:1) to GSK3772847 (10 mg/kg) or matching placebo intravenously administered at Weeks 0, 4, and 8, in addition to standard of care. Randomization was based on systemic anti-fungal treatment status at screening. Primary endpoints were change from baseline (Week 0) to Week 12 in blood eosinophils and fractional exhaled nitric oxide. Results Participants (n = 17) were randomized to GSK3772847 (n = 8) or placebo (n = 9) for 12 weeks and included in efficacy and safety analyses. This study was terminated early due to the high rate of screen failure, low enrollment, and unlikely feasibility of timely study completion. There were no differences observed in blood eosinophils or fractional exhaled nitric oxide between treatment arms. Target engagement was demonstrated by reductions in free soluble suppressor of tumorigenicity 2 levels in the GSK3772847 arm throughout the treatment period. No deaths occurred and no new safety signals were identified. Conclusions Lack of clinical benefits with GSK3772847 was likely due to the small sample size, highlighting the need for larger prospective studies.