D1.153 - Protocol for a randomized, 5-arm study to evaluate the combination of omalizumab and allergen immunotherapy in patients with asthma due to house dust mites

Allergen immunotherapy (AIT) is the only disease-modifying therapy for treating allergic diseases. In patients with house dust mite (HDM)-driven asthma, sublingual AIT (SLIT) has demonstrated a robust effect in terms of asthma control, number of exacerbations, and safety. This trial aims to evaluate the combined action of SLIT with omalizumab (OMZ), an anti-IgE monoclonal antibody indicated for the treatment of moderate-to-severe persistent allergic asthma in patients with moderate HDM-driven asthma. 

This is a randomized, 5-arms, open-label, multicentre interventional study of patients aged 18 to 65 with confirmed HDM-driven, controlled asthma (GINA 3 and 4). The study will compare outcomes of five treatment options (see Figure): (1) 300IR HDM SLIT tablet for two years; (2) OMZ for two years; (3) 300IR HDM SLIT tablet plus OMZ for two years; (4) 300IR HDM SLIT tablet plus OMZ for one year followed by only 300IR HDM SLIT tablet for one year; or (5) standard of care for asthma for two years. The primary endpoint will be the change in the mean daily dose of inhaled corticosteroids after 24 months of therapy vs. baseline. Secondary endpoints will include asthma control (evaluated via standardized questionnaires), evaluation of the quality of life, safety and tolerability during the entire treatment period. The study will analyse changes in serum markers during therapy and lung function parameters as exploratory objectives. Analyses will be performed according to a pre-specified statistical analysis plan. Clinicaltrials.gov identifier NCT06027073.

The study started in September 2024 and is currently recruiting. The inclusion period is expected to last ten months, and the trial will end in March 2028. A total of 150 patients are expected to be enrolled in the study (allocation 1:1:1:1:1). In all cases, after the two-year treatment, patients will be followed up for one additional year to evaluate the long-term effects of therapies after treatment cessation. 

The systematic evaluation of combination treatments is necessary to explore synergies among established therapies, with the objective of personalizing treatment options, expanding the number of potential beneficiaries, and potentially reducing risks and costs. This trial should also provide relevant information on, possible reductions in asthma medication, and effects on the risk of onset of severe HDM-driven asthma in these patients.