Anakinra for Inflammatory Pustular Skin Diseases
Condition: Sneddon-Wilkinson; Acrodermatitis Continua of Hallopeau; Pustular Psoriasis; Palmoplantar Pustulosis
MeSH terms: Acrodermatitis; Psoriasis
Intervention: Anakinra
Intervention description: 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/day at week 8.
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Anakinra; Pustular Psoriasis; Palmoplantar Pustulosis; DITRA; Subcorneal Pustular Dermatosis

Summary:

      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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

        1.1 Females and males, aged greater than or equal to 18.

        1.2 Patients must demonstrate active noninfectious inflammatory pustular skin lesions
        resembling pustular psoriasis and involving greater than or equal to 5% total body surface
        area, or palmoplantar involvement. Conditions may include, but are not be limited to,
        pustular psoriasis, Sneddon-Wilkinson disease, subcorneal pustular dermatosis, reactive
        arthritis, palmoplantar pustulosis, acrodermatitis continua of Hallopeau and palmoplantar
        pustular psoriasis.

        1.3 Patients must have histopathologic confirmation of epidermal neutrophilic pustular skin
        disease.

        1.4 If taking immunosuppressants, retinoids or anti-neutrophil therapy, participants must
        maintain stable doses of these medications during the 2 weeks prior to study initiation.

        1.5 Patients must have stable topical medication regimen for 2 weeks prior to study
        initiation.

        1.6 Patients must have normal organ and marrow function as defined below:

        leukocytes greater than or equal to 3,000/mcL

        absolute neutrophil count greater than or equal to1,500/mcL

        platelets greater than or equal to 100,000/mcL

        creatinine within normal institutional limits OR creatinine clearance greater than or equal
        to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

        1.7 Quantiferon tuberculosis (TB) Gold must be performed for screening for mycobacterium
        tuberculosis infection. However, a tuberculin skin test may be placed if the Quantiferon TB
        gold test is indeterminate. Patients must have a negative Quantiferon TB Gold (or
        tuberculin skin test) or evidence of appropriate treatment prior to study entry.

        1.8 Patients must be able to understand and sign a written informed consent document and
        complete study-related procedures and questionnaires.

        EXCLUSION CRITERIA

        2.1 Enrollment in any other investigational treatment study or use of an investigational
        agent, or has not yet completed at least 3 half-lives since ending another investigational
        device or drug trial.

        2.2 History of treatment with canakinumab within the 12 months prior to study initiation.

        2.3 History of anakinra use.

        2.4 History of phototherapy within 2 weeks prior to study initiation.

        2.5 Patients may NOT concurrently be on biologic therapy such as etanercept, adalimumab,
        alefacept, infliximab, rituximab or rilonacept. If there is a history of use of biologic
        agents, there must be a washout period of at least 3 half-lives prior to study initiation.

        2.6 Subjects who experience a significant flare after discontinuation of a tumor necrosis
        factor (TNF) inhibitor as part of this study that requires urgent medical management or
        hospitalization, or in the estimation of the principal investigator poses excessive risk to
        the patient to enter the study.

        2.7 Other defined dermatologic conditions which may include pustules as part of the
        clinical presentation, but which clinically and/or histologically do not resemble pustular
        psoriasis. Examples include, but are not limited to acute generalized exanthematous
        pustulosis (Acute generalized exanthematous pustulosis (AGEP), a drug-induced pustular
        dermatosis typically caused by beta-lactam antibiotics, tetracyclines, oral antifungals and
        other drugs), bacterial or fungal folliculitis, cutaneous candidiasis, tinea pedis, tinea
        corporis, neutrophilic eccrine hidradenitis or eosinophilic pustular folliculitis (Ofuji
        syndrome).

        2.8 Known diagnosis of Deficiency of the interleukin-1 receptor antagonist (DIRA).

        2.9 History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to anakinra or other agents used in study. Known hypersensitivity to Chinese
        hamster ovary (CHO)-cell derived biologics or any components of anakinra.

        2.10 Treatment with a live virus vaccine during the 3 months prior to baseline visit. No
        live vaccines will be allowed throughout the course of this study.

        2.11 Patients with active or untreated malignancy-- with the exception of cutaneous basal
        or squamous cell carcinomas, or in situ cervical carcinoma-- are ineligible because of the
        immunomodulating effects of anakinra. The risk of recurrent malignancy secondary to this
        drug is unknown.

        2.12 Presence of active infection. History of exposure to TB (positive purified protein
        derivative (PPD) or Quantiferon TB gold) who have not been treated with a TB prophylaxis
        regimen for at least one month.

        2.13 Chest x-ray demonstrating pleural scarring and/or calcified granuloma consistent with
        prior or current untreated TB.

        2.14 History of chronic or recurrent infection including but not limited to human
        immunodeficiency virus (HIV), hepatitis B or hepatitis C.

        2.15 Individuals with severe or uncontrolled recurrent cutaneous infections who are
        considered at elevated risk for serious infection on anakinra therapy will be excluded per
        physician discretion.

        2.16 Presence of other known significant autoimmune or inflammatory disease. Examples
        include major chronic infectious/inflammatory/immunologic diseases such as systemic lupus
        erythematosus, rheumatoid arthritis, Sjogren's syndrome and periodic fever syndromes.

        2.17 Other immunoregulatory or immunodeficiency diseases, such as multiple sclerosis.

        2.18 Individuals with life-threatening or disabling inflammation of the eyes, gut or joints
        requiring urgent or immediate medical attention, or at the physicians discretion.

        2.19 Subjects for whom there is concern about compliance with the protocol procedures.

        2.20 Uncontrolled intercurrent illness including, but not limited to, ongoing or active
        infection, uncontrolled or unmonitored psychiatric illness/social situations, or history of
        congestive heart failure, unstable angina pectoris or medically significant cardiac
        arrhythmia that would limit compliance with study requirements.

        2.21 Presence of other severe acute or chronic medical or psychiatric condition, or
        significant laboratory abnormality requiring further investigation that may cause undue
        risk for the subject's safety, inhibit protocol participation, or interfere with
        interpretation of study results, and in the judgment of the investigator would make the
        subject enrollment inappropriate.

        2.22 The effects of anakinra on the developing human fetus are unknown. Women of
        childbearing potential and men must agree to use adequate contraception (hormonal or
        barrier method of birth control or abstinence) prior to study entry and for the duration of
        study participation. Should a woman become pregnant or suspect she is pregnant while she or
        her partner is participating in this study, she should inform her treating physician
        immediately. Females of childbearing potential must have a negative serum pregnancy test at
        screening. Females must also have a negative serum pregnancy test at baseline and prior to
        performance of any radiologic procedure or administration of study medication and during
        each National Institutes of Health (NIH) visit. Lactating mothers will discontinue
        breastfeeding prior to study enrollment.

        2.23 Pregnant or lactating females. Women of non-childbearing potential is defined as women
        who are postmenopausal (no menses for > one year) or who have had a hysterectomy and will
        not require Beta-Human Chorionic Gonadotropin (B-HCG) testing