Safety, Tolerability, and Pharmacokinetics of Orally Inhaled DNAzyme Solution for Nebulisation in Healthy Male Subjects
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Asthma is a chronic inflammatory bronchial disorder with three distinct components: airway
hyper-responsiveness (respiratory hypersensitivity), airway inflammation, and intermittent
airway obstruction. One of the characteristics of the disease is an inflammatory reaction of
the immune system caused by cytokine production. A substantial number of asthma patients do
not satisfactorily respond to steroid therapy and consequently have an unmet medical need for
novel targeted therapies with improved specificity, tolerability, and compliance.
Novel therapeutic strategies for the treatment of chronic inflammatory diseases by targeting
early disease-causing mechanisms are a promising approach for the treatment of asthma. The
transcription factor GATA-3 plays a key role in mediating the asthmatic immune response and
has been shown to be necessary and sufficient for the production of cytokines interleukin
(IL)-4, IL-5, and IL-13. The active principle hgd40 of the investigational medicinal product
SB010 belongs to a new class of antisense oligonucleotide therapeutics, the 10-23 DNA
(deoxyribonucleic acid) zymes (antisense oligonucleotide). DNAzymes are catalytically active
nucleic acids that cleave complementary RNA (ribonucleic acid) molecules. By cleaving GATA-3
mRNA hgd40 reduces specific cytokine production and thereby reduces key features of allergic
airway inflammation.
DNAzymes are completely generated by chemical synthesis and can be produced under Good
Manufacturing Practice (GMP) controlled conditions. The DNAzymes are not biological drugs,
i.e. they are not generated by use of any living organism including cell culture or bacteria.
The molecules are highly water-soluble and will be applied as solution directly in their
synthesized form.
The current study will evaluate the safety and tolerability of increasing single doses of
inhaled SB010 in healthy male subjects.