A Study of ILV-94 (Anti-22 Antibody) Administered via IV in Atopic Dermatitis

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DESCRIPTION (provided by applicant): Atopic dermatitis (AD) is the most common inflammatory skin disorder, affecting up to 3-4% of adults and 25% of the children, most of which are part of the moderate-to-severe AD category, and which is extremely difficult to control. Currently there is a large unmet need for effective systemic treatment AD is associated with activation of Th2 and the recently described Th22 T-cell subsets, while unlike psoriasis, it has minimal Th17 component. In psoriasis neutralization of IL-17/Th17 by antibodies to IL-17A cytokine or to its receptor can lead to disease reversal in majority of treated subjects, with few adverse effects related to immune antagonism. We hypothesize that the newly discovered Th22, has a key pathogenic role in AD through the production of IL-22. IL-22 promotes epidermal hyperplasia and inhibits epidermal differentiation, which are major features of AD. Thus, we postulate that IL-22 is a "driver" cytokine in AD, analogous to IL-17 in psoriasis. ILV-094, a human IgGIA antibody that binds with high specificity to IL-22 is a potent neutralizer of IL 22 activity. Multiple studies showed that ILV-094 has favorable pharmacokinetics and toxicity profiles. This study is the first to explore the clinical and biological effects of blocking IL-22 n AD. Our specific aims are: 1 .To assess the safety, tolerability and clinical efficacy of intravenous (IV) administration of an IL-22 neutralizing antibody ILV-094 to subjects with moderate-to-severe AD; 2.To test the hypothesis that the abnormal epidermal hyperplasia and differentiation abnormalities in AD are attributable to IL-22 cytokine; and 3.To determine the impact of IL-22 blockade on suppression of Th2 and T22 activation. This is a placebo-controlled, double-blind, study of IV administration of ILV-094 / placebo to AD patients, assigned in a 2:1 ratio (active vs. placebo). A total of 6 IV doses will be administered over 10 weeks. Patients will be followed for 10 additional weeks. The clinical effects on AD disease activity will be evaluated by change in the Scoring of AD (SCORAD) and investigator's global assessment (IGA) indices at week 12. Biopsies and blood samples collected at baseline, and weeks 4 and 12, will be analyzed by immunohistochemistry, RTPCR and gene arrays.