Anakinra for Inflammatory Pustular Skin Diseases

This study is currently recruiting participants.
Verified October 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01794117
First received: February 15, 2013
Last updated: March 14, 2014
Last verified: October 2013
  Purpose

Background:

  • Inflammatory pustular skin diseases are a type of autoinflammatory disease in which the immune system attacks the body s 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.
  • 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.

Condition Intervention Phase
Pustular Dermatosis
Drug: Anakinra
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Anakinra in Inflammatory Pustular Dermatoses: Evaluation of Therapeutic Efficacy and Validation of PathogenicMechanisms

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Obtain an estimate of the response rate to treatment [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Optimal dosing and safety [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: January 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Anakinra
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA

Females and males, aged greater than or equal to 18.

Patients must demonstrate active noninfectious inflammatory pustular skin lesions resembling pustular psoriasis and involving (Bullet) 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.

Patients must have histopathologic confirmation of epidermal neutrophilic pustular skin disease.

If taking immunosuppressants, retinoids or anti-neutrophil therapy, participants must maintain stable doses of these medications during the 2 weeks prior to study initiation.

Patients must have stable topical medication regimen for 2 weeks prior to study initiation

Patients must have normal organ and marrow function as defined below:

leukocytes > 3,000/mcL

absolute neutrophil count > 1,500/mcL

platelets > 100,000/mcL

creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Patients must have either (1) a negative PPD test per CDC guidelines and no evidence of active TB on chest radiograph at the time of enrollment, or (2) a positive PPD with no evidence of active TB by history or on chest radiograph at the time of enrollment AND either past or present treatment with adequate therapy for at least one month prior to first dose of study medication.

Patients must be able to understand and sign a written informed consent document and complete study-related procedures and questionnaires.

EXCLUSION CRITERIA

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.

History of treatment with canakinumab within the 12 months prior to study initiation.

History of anakinra use.

History of phototherapy within 2 weeks prior to study initiation.

Patients may NOT concurrently be on biologic therapy such as etanercept, adalimumab, alefacept, infliximab, rituximab or rilonacept (Appendix A). 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.

Subjects who experience a significant flare after discontinuation of a 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.

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 (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).

Known diagnosis of DIRA.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to anakinra or other agents used in study. Known hypersensitivity to CHO-cell derived biologics or any components of anakinra.

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.

Pregnant or lactating females.

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.

Presence of active infection. History of exposure to TB (positive PPD) who have not been treated with a TB prophylaxis regimen for at least one month.

Chest x-ray demonstrating pleural scarring and/or calcified granuloma consistent with prior or current untreated TB.

History of chronic or recurrent infection including but not limited to HIV, hepatitis B or hepatitis C.

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.

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.

Other immunoregulatory or immunodeficiency diseases, such as multiple sclerosis.

Individuals with life-threatening or disabling inflammation of the eyes, gut or joints requiring urgent or immediate medical attention, or at the physician s discretion.

Subjects for whom there is concern about compliance with the protocol procedures.

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.

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.

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 urine 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 NIH visit. Lactating mothers will discontinue breastfeeding prior to study enrollment.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01794117

Contacts
Contact: Haley B Naik, M.D. (301) 594-3208 naikhb@mail.nih.gov
Contact: Edward W Cowen, M.D. (301) 496-4299 ec176r@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Edward W Cowen, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01794117     History of Changes
Other Study ID Numbers: 130071, 13-C-0071
Study First Received: February 15, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Efficacy
Optimal Dosing
Safety
Pustular Skin Lesion
Neutrophilic Pustulosis

Additional relevant MeSH terms:
Skin Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014