Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of the Topical Formulation SB011 Applied to Lesional Skin in Patients With Atopic Eczema
Condition: Mild to Moderate Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Study type: Interventional
Phase: Phase 2

Summary: 
      Atopic dermatitis (AD) is a chronic or chronic recurring inflammatory skin disorder. Patients
      suffer from eczema and often severe pruritus on the affected skin, as well as from frequent
      complications and secondary infections. Next to a genetically predetermined defect in
      epidermal barrier function and vegetative dysfunction, AD arises from an upregulation of
      Th2-modified immune responses inducing increased IgE-antibody production, cytokine secretion
      and subsequently, local inflammation.

      Although standard therapies of AD, modern topical corticosteroids, show a better ratio of
      therapeutic effects to side effects, they retain a moderate acceptance due to their
      non-specific action, strict compliance requirements and possible adverse effects. As a newer
      alternative, calcineurin inhibitors show fewer side effects but raise concerns regarding long
      term risks including the possibility of skin carcinogenicity. Therefore, medical need remains
      for novel therapies for this major public health problem, directed in particular at specific
      early disease-causing mechanisms and/or molecular targets, with an improved efficacy, safety
      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 AD.

      The transcription factor GATA-3 represents the key regulatory factor of Th2-driven immune
      responses. It is indispensable for the differentiation and activation of Th2 cells; it
      integrates Th2 signals and induces Th2 cytokine expression. The investigational product SB011
      contains the DNAzyme hgd40 that targets GATA-3. 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 a water/oil/water (W/O/W)
      formulation since multiple emulsions have been shown to protect the active ingredient from
      degradation on the skin and have penetration enhancing properties in comparison to other
      carrier systems.

      This proof-of-concept study will evaluate the efficacy, safety, tolerability,
      pharmacokinetics (PK), and pharmacodynamics (PD) of the topical formulation SB011 containing
      2 % hgd40 twice daily (BID) in patients with mild to moderate atopic eczema.
    


Intervention name(s): SB011, 2 % (Water/Oil/Water) emulsion of hgd40; Multiple W/O/W formulation, active ingredient-free vehicle
Intervention type(s): Drug; Drug
Intervention description(s): Treatment will be performed BID on 14 consecutive days and one single last application at the site on Day 15 (29 applications in total).
Two preferably disseminated and contralateral, comparable lesional treatment areas of approximately 50 cm2 each and located on arms, legs, chest, stomach or neck will be chosen. All patients will perform treatment with both formulation SB011 containing 2% hgd40 and the active ingredient-free vehicle. Comparison of the IMPs will be performed intraindividually.
Approximately 5 mg/cm2 (250 μl) of SB011 (2% hgd40) and the vehicle will be applied to the respective treatment areas. The time between the two applications should include min. 8 hours and max. 16 hours. Patients compliance will be controlled by weighing of the IMPs at each visit. On day 1 the application of the IMPs will be demonstrated to the patients at the clinical site. The first treatment as well as the morning treatment on Days 3, 5, 8, 12, and 15 will be carried out at the clinical site; Treatment will be performed BID on 14 consecutive days and one single last application at the site on Day 15 (29 applications in total).
Two preferably disseminated and contralateral, comparable lesional treatment areas of approximately 50 cm2 each and located on arms, legs, chest, stomach or neck will be chosen. All patients will perform treatment with both formulation SB011 containing 2% hgd40 and the active ingredient-free vehicle. Comparison of the IMPs will be performed intraindividually.
Approximately 5 mg/cm2 (250 μl) of SB011 (2% hgd40) and the vehicle will be applied to the respective treatment areas. The time between the two applications should include min. 8 hours and max. 16 hours. Patients compliance will be controlled by weighing of the IMPs at each visit. On day 1 the application of the IMPs will be demonstrated to the patients at the clinical site. The first treatment as well as the morning treatment on Days 3, 5, 8, 12, and 15 will be carried out at the clinical site
Other intervention name(s): Active drug substance is hgd40
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antisense oligonucleotide; atopic eczema; atopic dermatitis; Phase II; Transcription factor GATA-3; dermal application; Proof-of-Concept