A Phase 2 Study of Anakinra in Inflammatory Pustular Dermatoses: Evaluation of Therapeutic Efficacy and Validation of Pathogenic Mechanisms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Participants Treated With Anakinra Who Achieve 50% Disease Improvement by the End of Week 12, as Measured by Total Body Surface Area Involvement (TBSAI50)
研究概览
简要总结
Background:
- Inflammatory pustular skin diseases are a type of autoinflammatory disease in which the immune system attacks the bodys tissues. These diseases cause painful and itchy skin rashes, eye and mouth irritation, joint pain and fever. Several drugs for treating these diseases suppress the immune system. However, they can cause severe side effects when taken over a long period of time.
- Interleukin 1 (IL-1) is a small protein that may be important in causing the inflammation seen in pustular skin disease. Anakinra is a drug that works by blocking IL-1. It has been effective in treating some inflammatory conditions such as rheumatoid arthritis. However, anakinra has not been studied for use in patients with pustular skin disease. Researchers want to see whether anakinra will be effective in treating pustular skin disease.
Objectives:
- To see if anakinra can be used to treat inflammatory pustular skin disease.
Eligibility:
- Individuals at least 18 years of age who have inflammatory pustular skin disease.
Design:
- Participants will be screened with a physical exam and medical history. Their disease will be evaluated with blood tests, urine tests and imaging studies. Skin biopsies may also be collected.
- Participants will have an initial visit to receive the first dose of anakinra. They will be shown how to give themselves daily injections of anakinra.
- Participants will take anakinra for up to 12 weeks as long as there are no severe side effects. During this time, they will keep a study diary to record the severity of any rashes, pustules, itching, fevers, and skin or joint pain. They will bring this diary to their study visits.
- Participants will have study visits at weeks 4, 8 and 12. Treatment will be monitored at these visits with blood tests, urine tests and physical exams. Depending on the effects of the treatment, participants may have the dose of anakinra increased or decreased.
- Participants will have a final study visit 4 weeks after they stop taking anakinra.
详细描述
Background:
-
Inflammatory disorders that present with neutrophilic pustular skin lesions, including generalized pustular psoriasis, are characterized by severe cutaneous manifestations, generalized inflammation and significant morbidity.
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Recent studies in patients with phenotypically similar pustular diseases have identified two monogenic forms of neutrophilic pustular psoriasis implicating interleukin (IL)-1 in disease pathogenesis.
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Deficiency of the Interleukin 1 (IL-1) receptor antagonist (IL1RN, DIRA) is an autosomal recessive condition characterized by severe generalized pustular eruptions in the neonatal period, osteopenia, lytic bone lesions, joint pain, respiratory insufficiency, thrombosis, elevated acute phase reactants and significant mortality. Patients with this condition have responded rapidly to IL-1 receptor antagonist, anakinra.
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Deficiency of IL-36 receptor antagonist (IL-36RN/IL1F5, DITRA) is an autosomal recessive condition with episodic widespread pustular skin lesions, fevers and systemic inflammation defined by marked leukocytosis and elevated c-reactive protein.
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Both IL1RN and IL36RN/IL1F5 are highly expressed in epidermal keratinocytes, suggesting a role for keratinocytes in initiating innate immunity-mediated inflammatory skin diseases, and ultimately manifesting in a pustular phenotype.
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Patients with inflammatory pustular diseases often respond poorly to conventional treatment with methotrexate, cyclosporine and anti- tumor necrosis factor (TNF) agents.
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Two recent case reports describe patients with pustular psoriasis unresponsive to TNF inhibition who responded to anti-IL-1 receptor therapy with anakinra. We hypothesize that monogenic and polygenic inflammatory pustular skin diseases share common pathogenic mechanisms mediated by IL-1.
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We propose a phase 2 study that will utilize a collaborative bench-to-bedside approach, applying targeted anti-IL-1 therapy, novel imaging modalities, and laboratory techniques including immunohistochemistry, gene expression and cytokine studies, and in vitro manipulations of skin to dissect and validate pathways in these complex diseases.
Objectives:
-To characterize the clinical efficacy, optimal dosing and safety of anakinra in patients with pustular dermatoses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 110 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A/Anakinra 100 mg/day
An initial dose of anakinra 100 mg/day will be administered daily via self-administered subcutaneous injection. If active disease persists at this dose, anakinra dose may be escalated up to 200 mg/day injected subcutaneously daily at week 4 and 300mg at week 8.
干预措施: Anakinra (Drug)
结局指标
主要结局
Number of Participants Treated With Anakinra Who Achieve 50% Disease Improvement by the End of Week 12, as Measured by Total Body Surface Area Involvement (TBSAI50)
时间窗: 12 Weeks
Total Body Surface Area Involvement (TBSAI) is defined as the amount of total amount of active disease involvement on a given patient. 50% improvement was the amount of change that we judged at the start of the study would qualify as significant improvement.
次要结局
未报告次要终点
研究者
Edward Cowen, M.D.
Principal Investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)