Safety, Tolerability, and Pharmacokinetics After a Single Dose of Orally Inhaled DNAzyme Solution for Nebulisation in Male Patients With Asthma

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 drug substance of the investigational medicinal product SB010 is hgd40. 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 single doses of inhaled SB010 in male patients with asthma who have airway hyperresponsiveness(demonstrated by methacholine bronchial challenge test).

Conditions

• Asthma

Interventions

DRUG

SB010

Three consecutive ascending dose groups (A, B, and C) are planned, with a total of 24 patients with asthma. Each dose group will consist of 8 patients (n=6 receiving active drug and n=2 receiving placebo). Each patient will participate in one dose group only. Dose escalation to the second and third dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control, up to 4 hours after administration) of the preceding dose group by the Safety Board. Dose levels: Dose group A: 5 mg hgd40 in 2 mL solution (concentration: 2.5 mg/mL); Dose group B: 10 mg hgd40 in 2 mL solution (concentration: 5.0 mg/mL); Dose group C: 20 mg hgd40 in 2 mL solution (concentration: 10.0 mg/mL).

DRUG

Placebo

Three consecutive ascending dose groups (A, B, and C) are planned, with a total of 24 patients with asthma. Each dose group will consist of 8 patients (n=6 receiving active drug and n=2 receiving placebo). Each patient will participate in one dose group only. Dose escalation to the second and third dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control, up to 4 hours after administration) of the preceding dose group by the Safety Board.

Sponsors & Collaborators

• Sterna Biologicals GmbH & Co. KG

  lead INDUSTRY

Principal Investigators

• Jens Hohlfeld, Prof. Dr. · Clinical Airway Research Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-04-30

Primary Completion

2012-08-31

Completion

2012-08-31

Countries

• Germany

Study Locations