IVL745 is a potent and selective antagonist of the integrin VLA-4(₄ß₁). VLA-4 is involved in the extravasation, activation and extravascular survival of inflammatory cells at sites of airway inflammation. In animal models, IVL745 reduces airway inflammatory responses. Therefore IVL745 deserved investigation as a potential anti-inflammatory agent.

We examined the effects of IVL745 on the early (EAR) and late (LAR) asthmatic response to inhaled allergen, and on other markers of airway inflammation in a placebo controlled, double blind, randomised, two-way crossover study. We studied 16 subjects (2 female and 14 male), aged 18-60 (mean age 28.9) years with mild atopic asthma controlled with short acting beta₂ agonist alone, with a methacholine PC20 of less than 8mg/mL, and with EAR and LAR to inhaled allergen.

Subjects took 20 mg IVL745, or placebo, twice daily on Days 1-7 with a single dose on Day 8. Doses were given via an Ultrahaler metered-dose DPI. The subjects underwent the following procedures: Day 7 - induced sputum collection and exhaled nitric oxide (NO) measurement; Day 8 - inhaled allergen challenge; Day 9 - NO and methacholine challenge; Day 10 -induced sputum collection. Adverse events, PEFR, use of short-acting beta₂ agonist and symptoms were recorded throughout the study. Treatments were separated by at least two weeks' washout.

There was no difference between IVL745 and placebo in the effect of the LAR between 3 and 9 h after allergen challenge as measured by AUC of % change in FEV₁ from the pre-challenge baseline (Table 1) or by the maximum % change from the pre-challenge baseline (Table 2).

There was no difference between IVL745 and placebo with respect to EAR, NO, methacholine responsiveness, inflammatory cells or cytokines in induced sputum post allergen challenge (Day 9), symptom scores, PEFR or beta₂ agonist use. There was a statistically significant reduction in percentage of eosinophils in sputum on Day 7 (placebo mean 15.00, median, 12.65; IVL745 mean 7.32, median 4.00 (95 % CI of difference -13, -1.2 p=0.02).

In conclusion, IVL745 had no effect on markers of airways inflammation in patients with mild asthma, other than a slight reduction in sputum eosinophils.