A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Anakinra; Kineret; Atopic Dermatitis; Eczema; Allergic Disease
Intervention: Anakinra (Drug)
Phase: Phase 1
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Official(s) and/or principal investigator(s):
Joshua D Milner, M.D., Principal Investigator, Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
Michelle R O'Brien, R.N., Phone: (301) 443-8341, Email: firstname.lastname@example.org
- 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
- To assess the safety and effectiveness of using anakinra to treat severe atopic dermatitis
- Children between 10 and 18 years of age who have been diagnosed with severe atopic
dermatitis that has not responded to standard treatment.
- 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.
Official title: A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Improvement of Atopic Dermatitis symptoms without increase in serious infections; Response to treatment with a 30 percent decrease in SCORAD score.
Secondary outcome: 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.
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
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.
Minimum age: 10 Years.
Maximum age: 30 Years.
- INCLUSION CRITERIA:
To be eligible for enrollment in this protocol, participants must fulfill all of the
1. Must be 10 years to 30 years of age
2. Patient or legal guardian must be able to give informed consent
3. Must have evidence of severe atopic dermatitis as determined by the investigators and
a SCORAD score > 40 performed within 90 days of study entry
4. Must have report from primary physician documenting lack of sufficient response to
topical corticosteroids for > 6 months
5. Must have skin test or radioallergosorbent test (RAST) showing sensitivity to greater
than or equal to 3 food and/or airborne allergens
6. Must have a baseline CBC that demonstrates:
- White Blood Cell Count (WBC) greater than or equal to lower limit of normal for
- Absolute Neutrophil Count (ANC) greater than or equal to lower limit of normal
c. Platelet Count greater than or equal to lower limit of normal for age
7. Must not be pregnant or breastfeeding
8. If subject is a female that has begun menstruation, and is sexually active, she must
agree to consistently use contraception throughout study participation. Acceptable
forms of contraception are:
- Condoms, male or female, with spermicide
- Diaphragm or cervical cap with spermicide
- Intrauterine device
- Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved
- Male partner has previously undergone a vasectomy for which there is
documentation of aspermatogenic sterility
9. Must have a primary care physician
10. Must be willing to submit blood and skin tissue for storage
A patient will be ineligible to participate in this protocol if any of the following
criteria are fulfilled:
1. Patient is taking oral or injectable immunomodulators (such as methotrexate, imuran,
and cyclosporine) or biologics (such as etanercept or omalizumab).
2. Patient requires systemic immunosuppression at any time during the study
3. Patient has known diseases of immunodysregulation or immunodeficiency.
4. Any chronic medical condition other than atopic dermatitis, allergy/asthma and
infection, such as heart disease, diabetes and autoimmunity that, in the
investigator's opinion, places the patient at undue risk by participating in the
5. History of anaphylactic reaction or hypersensitivity to anakinra.
6. The presence of certain types of acquired abnormalities of immunity such as human
immunodeficiency virus (HIV), cytotoxic chemotherapy for malignancy could be grounds
for possible exclusion if, in the opinion of the investigator, the presence of such
disease process interferes with evaluating a coexisting abnormality of immunity that
is a subject of study under this protocol.
7. The presence of any dermatologic diagnosis which, in the investigator's opinion, is
not consistent with atopic dermatitis and would impair the ability to assess drug
8. Has a diagnosis of active tuberculosis with consistent findings from a PPD skin test,
computerized tomography (CT) scan or Chest x-ray. Those subjects found to have a
positive PPD will be referred back to their primary care physician for appropriate
9. Has received a live vaccine within 4 weeks prior to therapy or potential need for a
live vaccine during the study.
10. Is unwilling to undergo testing or procedures associated with this protocol.
11. The patient or guardian is unable or unwilling to give daily injections.
Locations and Contacts
Michelle R O'Brien, R.N., Phone: (301) 443-8341, Email: email@example.com
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL), Phone: 800-411-1222, Ext: TTY8664111010, Email: firstname.lastname@example.org
NIH Clinical Center Detailed Web Page
Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. Review.
Farshidi A, Sadeghi P. Successful treatment of severe refractory atopic dermatitis with efalizumab. J Drugs Dermatol. 2006 Nov-Dec;5(10):994-8.
Schmitt J, Schäkel K, Schmitt N, Meurer M. Systemic treatment of severe atopic eczema: a systematic review. Acta Derm Venereol. 2007;87(2):100-11. Review.
Starting date: April 2010
Last updated: December 8, 2012