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

Authors: Duong, M.¹; Cockcroft, D.²; Boulet, L.-P.³; Ahmed, T.⁴; Iverson, H.⁵; Atkinson, D. C.⁵; Stahl, E. G.⁵; Watson, R.¹; Davis, B.²; Milot, J.³; Gauvreau, G. M.¹; O'Byrne, P. M.¹

Source: Allergy, Volume 63, Number 9, September 2008 , pp. 1195-1201(7)

Publisher: Wiley-Blackwell

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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 [maxFEV₁% (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.

Keywords: anti-allergic; anti-inflammatory; asthma; heparin derivative

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1398-9995.2008.01707.x

Affiliations: 1: McMaster University, Hamilton, ON 2: University of Saskatchewan, Saskatoon, SK 3: Institut de cardiologie et de pneumologie de l'Université Laval, Hôpital Laval, Québec, QC, Canada 4: Mount Sinai Medical Centre, Miami Beach 5: IVAX Research Inc., Miami, FL, USA

Publication date: 2008-09-01

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

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