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Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma.
J Allergy Clin Immunol 2005; 116(4):761-7JA

Abstract

BACKGROUND

Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease.

OBJECTIVE

We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation.

METHODS

The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting beta2-agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting beta2-agonists, and asthma symptoms were recorded daily throughout the study.

RESULTS

There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV1 from the prechallenge baseline (mean [SEM], -81.99 [18.80] after IVL745 and -72.58 [21.29] after placebo; 95% CI of difference, -36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], -23.44 [4.73] after IVL745 and -21.30 [5.17] after placebo; 95% CI of difference, -11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, -13 to -1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled beta2-agonist use, or PEF.

CONCLUSION

In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils.

Authors+Show Affiliations

Hammersmith Medicines Research, Central Middlesex Hospital, London, United Kingdom. vnorris@hmrlondon.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16210048

Citation

Norris, Virginia, et al. "Effect of IVL745, a VLA-4 Antagonist, On Allergen-induced Bronchoconstriction in Patients With Asthma." The Journal of Allergy and Clinical Immunology, vol. 116, no. 4, 2005, pp. 761-7.
Norris V, Choong L, Tran D, et al. Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma. J Allergy Clin Immunol. 2005;116(4):761-7.
Norris, V., Choong, L., Tran, D., Corden, Z., Boyce, M., Arshad, H., ... Kirkesseli, S. (2005). Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma. The Journal of Allergy and Clinical Immunology, 116(4), pp. 761-7.
Norris V, et al. Effect of IVL745, a VLA-4 Antagonist, On Allergen-induced Bronchoconstriction in Patients With Asthma. J Allergy Clin Immunol. 2005;116(4):761-7. PubMed PMID: 16210048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma. AU - Norris,Virginia, AU - Choong,Lee, AU - Tran,Duyen, AU - Corden,Zoe, AU - Boyce,Malcolm, AU - Arshad,Hasan, AU - Holgate,Stephen, AU - O'Connor,Brian, AU - Millet,Sylvaine, AU - Miller,Barry, AU - Rohatagi,Shashank, AU - Kirkesseli,Stephane, Y1 - 2005/08/19/ PY - 2004/10/18/received PY - 2005/04/03/revised PY - 2005/04/08/accepted PY - 2005/10/8/pubmed PY - 2005/12/13/medline PY - 2005/10/8/entrez SP - 761 EP - 7 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 116 IS - 4 N2 - BACKGROUND: Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease. OBJECTIVE: We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation. METHODS: The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting beta2-agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting beta2-agonists, and asthma symptoms were recorded daily throughout the study. RESULTS: There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV1 from the prechallenge baseline (mean [SEM], -81.99 [18.80] after IVL745 and -72.58 [21.29] after placebo; 95% CI of difference, -36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], -23.44 [4.73] after IVL745 and -21.30 [5.17] after placebo; 95% CI of difference, -11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, -13 to -1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled beta2-agonist use, or PEF. CONCLUSION: In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/16210048/Effect_of_IVL745_a_VLA_4_antagonist_on_allergen_induced_bronchoconstriction_in_patients_with_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(05)01489-2 DB - PRIME DP - Unbound Medicine ER -