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

ILV-94（抗 22 抗体）静脉注射治疗特应性皮炎的研究

• 批准号: 8580222
• 负责人: Emma Guttman
• 金额: $ 63.15万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8580222
• 关键词: Adult; Adverse effects; Affect; Antibodies; Atopic Dermatitis; Binding; Biological; Biological Markers; Biological Models; Biopsy; Blood specimen; Categories; Child; Clinical; Clinical Trials; Coupled; Coupling; Data; Disease; Disease remission; Dose; Double-Blind Method; Down-Regulation; Drug Kinetics; Elements; Event; Future; Genes; Human; Hyperplasia; Immune; Immune Targeting; Immunohistochemistry; Inflammation; Inflammatory; Institutional Review Boards; Interleukin-17; Intervention; Intravenous; Lead; Life; Measures; Molecular; Monoclonal Antibodies; Outcome; Outcome Measure; Pathogenesis; Pathway interactions; Patients; Pharmacodynamics; Phase; Phenotype; Placebo Control; Placebos; Production; Proteins; Psoriasis; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Safety; Skin; Specificity; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Therapeutic; Tissues; Toxic effect; base; clinical effect; clinical efficacy; cytokine; disease phenotype; indexing; inflammatory modulation; insight; interleukin-22; intravenous administration; keratinocyte; neutralizing antibody; novel; placebo controlled study; public health relevance; receptor; response; skin disorder; skin lesion; therapeutic development; therapeutic target; translational study

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.

描述（由申请人提供）：特应性皮炎（AD）是最常见的炎症性皮肤疾病，影响多达3-4％的成人和25％的儿童，其中大多数是中度至重度AD类别的一部分，这是极难控制的。当前，有效的全身治疗AD的未满足需要与TH2的激活和最近描述的Th22 T细胞亚群有关，而与牛皮癣不同，它的Th17成分最小。在通过对IL-17A细胞因子或其受体抗体对IL-17/TH17中和的牛皮癣中，可以导致大多数治疗受试者的疾病逆转，而与免疫拮抗作用相关的不良反应很少。我们假设新发现的Th22通过生产IL-22在AD中具有关键的致病作用。 IL-22促进表皮增生并抑制表皮分化，这是AD的主要特征。因此，我们假设IL-22是AD中的“驱动器”细胞因子，类似于牛皮癣的IL-17。 ILV-094，一种与IL-22高特异性结合的人IgGIA抗体是IL的有效中和 22活动。多项研究表明，ILV-094具有有利的药代动力学和毒性谱。这项研究是第一个探索阻断IL-22 N AD的临床和生物学作用的研究。我们的具体目的是：1。用于评估静脉内（IV）对中和抗体对中和中度AD受试者的IL-22中和抗体ILV-094的安全性，耐受性和临床功效； 2.检验以下假设：AD中异常表皮增生和分化异常归因于IL-22细胞因子； 3.确定IL-22阻断对TH2和T22激活抑制的影响。这是一项安慰剂对照，双盲的研究，对以2：1的比例分配给AD患者的IV-094 /安慰剂给药（主动与安慰剂）。总共将在10周内服用6次IV剂量。患者会 再持续10个星期。将通过在第12周的AD（SCORAD）和研究者的全球评估（IGA）评估（IGA）评分来评估对AD疾病活动的临床影响。免疫组织化学，RTPCR和基因阵列。