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


Intervention name(s): SB010; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antisense oligonucleotide; Asthma; Healthy subjects; Phase 1; Transcription factor GATA-3; Oral inhalation