Effect of Benralizumab in Atopic Dermatitis

Dermatitis, Atopic Clinical Trial

Official title: Benralizumab Regulates Atopic Dermatitis Through Effects on Eosinophils, Basophils and Innate Lymphoid Type 2 Cells.

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis, Atopic
• Eczema
• Genetic Diseases, Inborn
• Hypersensitivity
• Hypersensitivity, Immediate
• Immune System Diseases
• Skin Diseases
• Skin Diseases, Eczematous
• Skin Diseases, Genetic

• NCT number: NCT03563066
• Study type: Interventional
• Source: McMaster University
• Status: Completed
• Phase: Phase 2
• Start date: September 4, 2018
• Completion date: September 28, 2021