Effect of Benralizumab in Atopic Dermatitis
Condition: Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases
MeSH terms: Dermatitis, Atopic; Genetic Diseases, Inborn; Skin Diseases, Genetic; Dermatitis; Skin Diseases; Skin Diseases, Eczematous; Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate
Study type: Interventional
Phase: Phase 2

Summary: 
      Atopic Dermatitis (AD), also known as eczema, is a common skin disease characterized by itchy
      lesions. The prevalence of AD has increased over the past few decades, with 15-30% of
      children and 2-10%of adults being affected. The lesions of AD patients are very inflamed,
      with an increased number of inflammatory cells in the skin. There are not many medications
      available that are fully effective and can be used long-term for treatment of atopic
      dermatitis. Benralizumab is a monoclonal antibody used for treatment of a type of asthma
      called "eosinophilic asthma". Atopic dermatitis is also associated with elevated levels of
      eosinophils, and we would like to determine if benralizumab is effective in patients with
      atopic dermatitis. This is a randomized, double-blind, parallel group, placebo-controlled
      study will evaluate the effect of 3 doses of a fixed 30 mg dose of benralizumab administered
      subcutaneously (SC) every 4 weeks to patients with moderate-to-severe atopic dermatitis, on
      the severity of atopic dermatitis, and the cellular inflammation of skin lesions in these
      patients. Anti-inflammatory properties of benralizumab when a skin flare is induced in a
      controlled laboratory setting, in addition to the effects of benralizumab on skin that is
      already inflamed will be examined.It is hypothesized that benralizumab will attenuate
      eosinophilic inflammation in the skin.
    

Detailed description: 
      Patients with a history of moderate-to-severe atopic dermatitis will enter a screening period
      (Days -3 to -1) to assess responses to intradermal allergen challenge. Those developing a
      late cutaneous response 24 hours post-intradermal allergen challenge will be recruited for
      the study and have the size of the wheal/flare measured. A punch biopsy obtained from the
      challenge site and samples of peripheral blood and skin lesions will be obtained. Prior to
      randomization, skin lesions will be graded using the validated Eczema Area and Severity Index
      (EASI) Score as a baseline measure of the severity of disease. Patients will then be
      randomized 1:1 to benralizumab (30 mg SC monthly) or placebo, with dosing at days 0, 28 and
      56 (± 3 days). On Day 64 (1 week after the last dose of study drug), an intradermal allergen
      challenge will be conducted to determine the effect of benralizumab on allergen-induced
      responses in skin. On Day 65 (24 hours post-intradermal allergen challenge), the size of the
      wheal/flare will be measured and a punch biopsy will be obtained from the challenge site and
      samples peripheral blood and skin lesions will be obtained. Skin lesions will be reassessed
      clinically on Day 65 using the EASI score to assess the effect of benralizumab on changes to
      the severity of disease. A safety followup visit will take place at week 20, which is 140
      days after the first dose (12 weeks after the last dose/11 weeks after the last study
      procedure).

      Primary endpoint

      1. The number of eosinophils per millimetre squared of skin, measured 24 hours post
      intradermal allergen challenge, 65 days after the first dose. The number of eosinophils in
      the skin will be assessed by histological examination of a punch skin biopsy obtained from
      the site of the intradermal allergen challenge.

      Secondary endpoints

        1. The number of basophils per millimetre squared of skin, measured 24 hours post
           intradermal allergen challenge, after 65 days of dosing. The number of basophils in the
           skin will be assessed by immunohistochemistry of a punch skin biopsy obtained from the
           site of the intradermal allergen challenge, using a commercial antibody specific for
           basophils.

        2. The size of the late cutaneous response, measured 24 hours post intradermal allergen
           challenge, 65 days after the first dose. The late cutaneous response will be calculated
           using the length and width of the wheal and flare response to a standardized amount of
           allergen extract.

        3. Eczema Area and Severity Index (EASI) score.

      Exploratory endpoints

      1. The number of eosinophils, basophils, eosinophil progenitors, innate lymphoid cell type 2
      (ILC2s), cluster of differentiation (CD4+) T cells and hemopoietic cells in skin lesions
      after 65 days of dosing. The number of cells in skin lesions will be assessed by flow
      cytometry following digestion of the biopsy and staining with a validated panel of
      antibodies.
    

Intervention name(s): Benralizumab; Placebo Control
Intervention type(s): Drug; Drug
Intervention description(s): Subcutaneous benralizumab injections once per month for 3 months on Days 0, 28 & 56.; Subcutaneous placebo injections once per month for 3 months on Days 0, 28 & 56.
Intervention MeSH terms: Benralizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Skin Lesions; Benralizumab; Eosinophils; Intra-dermal challenge; Anti-inflammatory agents; Physiological Effects of Drugs