Safety profile and pharmacokinetics of an inhaled GATA-3-specific DNAzyme in a phase Ib study in patients with stable allergic asthma

SB010 (a nebulization solution of the human GATA-3-specific DNAzyme hgd40) has been developed for treatment of Th2-driven asthma. DNAzymes are single-stranded catalytic DNA molecules that specifically bind and cleave target mRNAs. Single or multiple applications of SB010 were already proven to be safe in Phase Ia studies in healthy subjects. Aim of this study was to investigate safety, tolerability and pharmacokinetics of inhaled single ascending doses of SB010 in a Phase Ib clinical trial in male stable allergic asthma patients with airway hyperresponsiveness (PC20 methacholine <= 4 mg/mL). The study was performed as a randomized, double-blind, placebo controlled, parallel group (per dose level) dose-escalation study in 24 patients (18-45 years). SB010 was applied as nebulized solution via a controlled breathing system (AKITA2APIXNEB®) in 3 dose levels (5, 10, 20 mg). Adverse events (AEs), vital signs, clinical chemistry, hematology, urinalysis, ECG, pulmonary function testing, body temperature, and overall tolerability were assessed. Generally, all dose levels were well tolerated. No clinically relevant influence on safety laboratory parameters, vital signs including lung function tests, differential blood count, or ECG measurements was observed. Plasma concentrations were analyzed using a hgd40-specific hybridization ELISA system. Maximum plasma concentrations of hgd40 were detected within the highest dose group at 1 hour after administration (13.51 ± 17.02 pg/mL); hgd40 was no longer detectable at 6 hours after administration. SB010 is now under evaluation in a phase IIa study.