The effect of IVX-0142, a heparin-derived hypersulfated disaccharide, on the allergic airway responses in asthma

M. Duong, D. Cockcroft, L. P. Boulet, T. Ahmed, H. Iverson, D. C. Atkinson, E. G. Stahl, R. Watson, B. Davis, J. Milot, G. M. Gauvreau, P. M. O'Byrne

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: IVX-0142 is a heparin-derived hypersulfated disaccharide devoid of anticoagulant activity while possessing anti-allergic and anti-inflammatory activity in preclinical studies. In a proof-of-concept study, the allergen inhalation challenge model was used to investigate the effect of IVX-0142 in mild atopic asthma. Methods: Nineteen subjects, not on controller medications, were randomized to an evaluator-blind, placebo-controlled, cross-over study. The effect of a single nebulized dose of IVX-0142 (80 mg) or placebo administered 30 min prior to allergen inhalation was evaluated on the allergic airway responses, airway responsiveness, and airway inflammation. Results: When compared with placebo, 14 and 13 subjects experienced a relatively smaller maximum fall in forced expiratory volume in 1 s (maxFEV1%) for the early airway response (EAR) and late airway response (LAR) with IVX-0142, respectively (P < 0.01). The degree of attenuation in the EAR [maxFEV 1% (mean ± SE) 26.5 ± 2.8% vs placebo 31.0 ± 2.8%, P = 0.059] and LAR (15.6 ± 2.9% vs placebo 19.0 ± 2.9%, P = 0.24) with IVX-0142, however, was small and did not reach statistical significance compared with placebo. Similarly, a trend in the attenuation of allergen-induced increase in the absolute sputum cell counts was also observed. No difference in the allergen-induced increase in airway hyper-responsiveness and exhaled nitric oxide was noticed. Conclusions: The majority of mild atopic asthmatics demonstrated a reduction in the EAR and LAR to IVX-0142. However, the treatment effect observed with a single prechallenge dose of IVX-0142 was small and heterogeneous. The potential anti-allergic and anti-inflammatory effects using multiple higher doses need to be evaluated.

Original languageEnglish (US)
Pages (from-to)1195-1201
Number of pages7
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume63
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Anti-allergic
  • Anti-inflammatory
  • Asthma
  • Heparin derivative

ASJC Scopus subject areas

  • Immunology

Fingerprint

Dive into the research topics of 'The effect of IVX-0142, a heparin-derived hypersulfated disaccharide, on the allergic airway responses in asthma'. Together they form a unique fingerprint.

Cite this