RT Journal Article
SR Electronic
T1 Late-breaking abstract: Attenuation of allergen-induced asthmatic responses by inhaled GATA-3 specific DNAzyme
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2816
VO 44
IS Suppl 58
A1 Holger Garn
A1 Norbert Krug
A1 Jens Hohlfeld
A1 Anne-Marie Kirsten
A1 Oliver Kornmann
A1 Kai Beeh
A1 Dominik Kappeler
A1 Stephanie Korn
A1 Stanislav Ignatenko
A1 Cordelia Rogon
A1 Joachim Bille
A1 Ursula Homburg
A1 Agnieszka Turowska
A1 Roland Buhl
A1 Jonas Renz
A1 Harald Renz
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P2816.abstract
AB BackgroundThe most prevalent phenotype of asthma is characterized by a TH2-driven eosinophil dominated inflammation. Therapeutic targeting of GATA-3, the master transcription factor of the TH2 pathway, may be beneficial. We evaluated the safety and efficacy of a novel DNAzyme specifically directed against GATA-3 mRNA (SB010).MethodsIn this randomized, double-blind, placebo-controlled, multicenter clinical trial, patients with allergic asthma with sputum eosinophilia exhibiting a biphasic early and late phase asthmatic response (EAR and LAR, respectively) following specific allergen provocation were assigned to receive 10 mg SB010 (N=21) or placebo (N=19) by inhalation once daily for 28 days. Allergen challenge was performed before and after treatment. Change in the area under the FEV1 curve (AUC) in LAR was the primary endpoint.ResultsSB010 attenuated the decline in mean FEV1 AUC by 34% compared with a 1% worsening in the placebo group (P=0.02) during LAR and by 11% compared with a 10% worsening in the placebo group during EAR (P=0.03). These effects were more pronounced in pre-specified subgroups of patients with blood eosinophils ≥ 4% (improvement LAR 41.7%, P=0.05; improvement EAR 28.3%, P=0.02) or FeNO ≥ 40 ppb. Lung function improvement was associated with changes in various TH2 pathway related biomarkers, including serum periostin, sputum eosinophils, eosinophilic cationic protein, and mast cell tryptase. No serious treatment emergent adverse events were reported.ConclusionsSB010 treatment significantly attenuated both LAR and EAR following allergen provocation. Biomarker analysis revealed a strong effect on TH2 regulated inflammatory responses (Clinical Trials NCT 01743768).