Atopic dermatitis (AD) is an inflammatory skin disease affecting as much as 20% of the population in western industrial societies. Chronic eczema in AD and associated pruritus can be a significant cause of morbidity and impact life quality. Disease pathogenesis is complex but ultimately converges on a pathological inflammatory process that disrupts the protective barrier function of the skin.
The prototypical inflammatory cytokine IL-1⍺ plays a key role in the pathophysiology of a wide range of inflammatory skin disorders1. MABp1 is a natural human antibody that exhibits immunoregulatory activity through blocking IL-1⍺ activity. Keratinocytes are a major reservoir of IL-1⍺ and may be a key source of inflammatory stimulus in AD. IL-1⍺ is present on leukocytes, where its role in leukocyte trafficking and infiltration may represent a key step in the chronic inflammation of AD. IL-1⍺ is a key inducer of matrix metalloproteinases activity which could be directly involved in the epithelial barrier breakdown in AD2. Loss of regulation of IL-1 results in systemic inflammation with extensive skin involvement3.
In previous dermatology studies MABp1 was well tolerated and showed impressive therapeutic activity4,5,6. Dose ranging of the subcutaneous formulation of MABp1 is now being studied in a 4 week open label treatment regimen for AD in order to establish the basis for further randomized studies.
The phase 2, open label, dose escalation multicenter study will consist of two dose cohorts of MABp1 in patients with moderate to severe AD. Ten patients will receive a total of 4 weekly subcutaneous injections of MABp1 at a dose of 200mg. Following a safety assessment for patients in the first dose cohort, ten patients will receive 4 weekly subcutaneous injections of MABp1 at a dose of 400mg. Patients will be followed for 6 weeks to allow for assessment of safety and preliminary efficacy. Various efficacy measures will be assessed including changes in Eczema Area and Severity Index Score (EASI), Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM) and SCORing Atopic Dermatitis (SCORAD), a measure of disease severity in AD.
You can find more information on this study by visiting www.clinicaltrials.gov