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A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis

Phase 1
Terminated
Conditions
Atopic Dermatitis
Eczema
Allergic Disease
Kineret
Anakinra
Registration Number
NCT01122914
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

Background:

* Severe atopic dermatitis, also known as eczema, is a chronic inflammatory skin condition that affects both children and adults and causes severe itching and skin redness. Current treatments of atopic dermatitis include topical creams and lotions, light therapy, and medications. However, the difficulty with long-term treatment for the chronic and severe nature of the disease requires more effective and better-tolerated therapeutic options.

* Anakinra is a drug that blocks a substance called interleukin-1 (IL-1), which may be important in causing the inflammation in atopic dermatitis. Researchers are interested in determining whether anakinra can be used to help treat atopic dermatitis. Anakinra has been approved by the Food and Drug Administration to treat rheumatoid arthritis in adults and children, but it has not been approved for use in adults or children with atopic dermatitis and is considered an experimental treatment in this study. In this study Anakinra will be administered as an injection under the skin every day for 3 months

Objectives:

- To assess the safety and effectiveness of using anakinra to treat severe atopic dermatitis in children.

Eligibility:

- Children between 10 and 18 years of age who have been diagnosed with severe atopic dermatitis that has not responded to standard treatment.

Design:

* Initial Screening: Participants will have an initial screening visit with a complete physical examination and medical history, blood and urine tests, photographs of the skin ,skin biopsy, and other tests as required.

* Run-in Period: At the screening visit, participants will receive a diary card and will be asked to track their atopic dermatitis symptoms on standard treatment for 2 months.

* Start of Treatment: At the end of the 2 month Run-in period participants will return for an inpatient visit (2 days) to receive the initial dose of anakinra and will be watched for any side effects. During the inpatient visit, participants will have additional examinations and blood and urine tests, and will be instructed on how to administer the anakinra injections at home.

Treatment Period: - Participants will return once a week for the first 2 weeks of treatment, at the end of the first month, and then once a month for the following 2 months, for a physical exam and blood tests. Participants will be asked to record symptoms related to their atopic dermatitis, anakinra administration and any side effects related to the anakinra on the diary card. The diary cards will be reviewed and collected at each visit.-

End of Treatment Period: At the end of 3 months of treatment with anakinra, participants will again be asked to record symptoms related to their atopic dermatitis on the diary card. Participants will be seen once a month for 3 months for a physical exam, blood tests and review of the diary card. . The final study visit will take place at the end of the 3rd month and will include a physical exam, blood tests, photographs and skin biopsy.

Detailed Description

Severe refractory atopic dermatitis is a chronic inflammatory pruritic skin condition that affects both children and adults. The disease is marked by periods of exacerbation and remission. Symptoms of atopic dermatitis may resolve by adolescence; however, it is estimated that the disease may persist in 50 percent of affected children well into adulthood.

Current possible treatments of atopic dermatitis include the use of topical corticosteroids, calcineurin inhibitors, phototherapy, as well as systemic medications i.e., methotrexate, cyclosporine, azathioprine, mycophenolate mofetil and interferon gamma. The difficulty with long-term treatment of this disease lies in its chronic nature associated with severe episodes. The combination of chronicity and severity of episodes of this diseases demands more effective and better-tolerated therapeutic options than those that are currently available. While the pathways of allergic inflammation are different than those of other inflammatory conditions, certain elements may overlap, providing targets for immune modulation. One of these targets is the interleukin-1 (IL-1) receptor.

The IL-1 receptor plays an important role in the development and maintenance of Th2 responses. Genetic, in vivo and in vitro data demonstrate a significant role for IL-1 signaling allergic and skin inflammatory conditions. This pilot study is therefore designed to assess the safety and efficacy of IL-1ra, a natural inhibitor of the IL-1 receptor, in disrupting atopic pathophysiologic pathways. Specifically, we will treat severe refractory atopic dermatitis associated with evidence of multiple specific allergic sensitivities. Up to 8 patients ages 10-30 with severe refractory dermatitis will be enrolled. Patients will be initially evaluated to establish the diagnosis of severe refractory AD as evidenced by SCORAD score greater than 40, followed by a 2 month (8 week) run-in period, a 3 month (12 week) treatment period of 3mg/kg/day anakinra given subcutaneously, followed by a 3 month (12 week) post-treatment evaluation period. In order to be considered evaluable for response, patients must have received a minimum of 67 out of 84 doses (80 percent) of anakinra. The primary endpoint is lack of an increase in serious infections, the secondary endpoint is a reduction of 30 percent or more in SCORAD score, and tertiary endpoints are cellular phenotypic and cytokine responses to IL-1 receptor blockade in atopic patients.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Improvement of Atopic Dermatitis symptoms without increase in serious infections; Response to treatment with a 30 percent decrease in SCORAD score.2 years
Secondary Outcome Measures
NameTimeMethod
Determine immunological phenotype and cytokine profile of peripheral blood before and after treatment with Anakinra; Determine impact of IL-1 r neutralization on total and antigen specific allergen sensitivity.2 years

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

🇺🇸

Bethesda, Maryland, United States

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