Safety, Tolerability, and Pharmacokinetics After a Single Dose of Orally Inhaled DNAzyme Solution for Nebulisation in Male Patients With Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

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).
    


Intervention name(s): SB010; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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).; 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.
Other intervention name(s): The active drug substance of SB010 is hgd40.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antisense oligonucleotide; Asthma; Patients with asthma; Phase 1b; Transcription factor GATA-3; Oral inhalation