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

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.

Conditions

• Asthma

Interventions

DRUG

SB010

Six ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour. Dose level (DL) 1: 0.4 mg hgd40/2 mL; DL 2: 2 mg hgd40/2 mL; DL 3: 5 mg hgd40/2 mL; DL 4: 10 mg hgd40/2 mL; DL 5: 20 mg hgd40/2 mL; DL 6: 40 mg hgd40/2 mL.

DRUG

Placebo

Six ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour.

Sponsors & Collaborators

• Sterna Biologicals GmbH & Co. KG

  lead INDUSTRY

Principal Investigators

• Wolfgang Timmer, MD · CRS-Mannheim GmbH, Germany

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-11-30

Primary Completion

2011-12-31

Completion

2011-12-31

Countries

• Germany

Study Locations