Clinical trial NCT01441076
Conditions: Autoimmune Connective Tissue Disorder Immune System Diseases
Keywords: Behcet's Disease Aphthous Ulcer Uveitis IL-1 Autoinflammation BD
Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Start date: 2011-09-01; Completion date: 2014-11-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- Behcet's disease (BD) is an autoimmune disease where the immune system attacks the body. People with BD may develop oral or genital ulcers, skin problems, and eye disease. Most drugs used to treat BD suppress the immune system, but they are not always helpful and may have side effects. A new drug, anakinra, may be able to treat BD with fewer side effects. Because it has not been studied in people with BD, anakinra is considered an experimental treatment.

Objectives:

\- To test whether anakinra can be a safe and effective treatment for Behcet s disease.

Eligibility:

\- People who have Behcet's disease with ongoing oral or genital ulcers for at least one month, or three or more flares of eye disease in the past 6 months.

Design:

* Participants will be screened with a physical exam and medical history. They will also have blood and urine tests. They will be divided into two groups: those with oral or genital ulcers and those with eye disease.
* All participants will keep a diary of symptoms for a month before starting the study drug.
* Participants with oral or genital ulcers will receive daily injections of anakinra for 3 to 6 months. Treatment will be monitored with frequent blood draws and daily diaries. Those who improve but do not have a full response to the drug may receive a higher dose. Those who improve after 6 months may have an extra 6 months on either anakinra or placebo to study the differences in response.
* Participants with eye disease will receive anakinra for up to 12 months. Treatment will be monitored with frequent blood draws, daily diaries, and regular eye exams.
* All participants will have a final study visit 1 month after stopping the study drug.

Detailed description:
Autoinflammatory diseases are illnesses characterized by episodes of inflammation that, unlike autoimmune disorders, lack the production of high titer autoantibodies or antigen-specific T cells. There is growing genetic and clinical evidence that Interleukin-1 (IL-1) plays a pathogenic role in several of these diseases. This exploratory study aims to examine the utility of anakinra in the treatment of adult subjects with Behcet s Disease (BD), a disease which shows similarities to the known anakinra-responsive autoinflammatory disorders, familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS). Anakinra is a recombinant form of the human interleukin-1 receptor antagonist that has been studied in rheumatoid arthritis (RA) and the autoinflammatory disorders. It has a half life of 4 to 6 hours with a FDA approved recommended dose of 100 mg/day subcutaneously for the treatment of rheumatoid arthritis.

This pilot study is designed to address: 1) the utility of anakinra in the treatment of BD; 2) the effect of anakinra on laboratory biomarkers in BD; and 3) an exploratory assessment of the safety of anakinra in individuals with Behcet's Disease.

Subjects with oral or genital ulcers will receive anakinra for three to six months. If five of the initial seven patients have a positive response, up to 20 patients with oral or genital ulcers will then be randomized to withdrawal or continuation of drug for six months once placebo is available. Patients with eye disease will be treated with anakinra for a total of twelve months without randomization to withdrawal. Clinical and biochemical correlates of inflammation will be measured at appropriate intervals to assess response and to further understand disease mechanisms.

Arms: arm 1: Treatment with Anakinra 100mg subcutaneous daily with option to escalate dose up to 300mg subcutaneous daily
Interventions: intervention 1: Anakinra
Intervention descriptions: intervention 1: Anakinra/Kineret\[registered\] is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra)

Protocol documents: