NCT01554319

Safety, Tolerability, and Pharmacokinetics After Multiple Doses of Orally Inhaled DNAzyme Solution for Nebulisation in Healthy Male Subjects

Phase-I Study in Healthy Male Subjects to Investigate Safety, Tolerability and Pharmacokinetics of Orally Inhaled Multiple Doses of SB010, a Human GATA-3-specific DNAzyme Solution for Nebulisation

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Sterna Biologicals GmbH & Co. KG · Industry
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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 generated completely 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 multiple doses of inhaled SB010 in healthy male subjects.

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	SB010	Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo). Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board. Dose group A : 5 mg hgd40/2 mL; Dose group B: 10 mg hgd40/2 mL; Dose group C: 20 mg hgd40/2 mL.
DRUG	Placebo (phosphate-buffered saline)	Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo). Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board.

Timeline

• Start date: 2012-04-01
• Primary completion: 2012-08-01
• Completion: 2012-08-01
• First posted: 2012-03-14
• Last updated: 2012-11-27

Locations

1 site across 1 country: Germany