A Pilot Study of XOMA 052 in Familial Cold Autoinflammatory Syndrome / Muckle-Wells Syndrome and Behcet's Disease
- Autoinflammatory diseases are illnesses that produce episodes of inflammation such as fever, rash, or joint swelling. Some of these diseases can be treated with medications that block the body's reaction to a protein called IL-1, which may be part of the cause of the inflammation. IL-1 blocking agents are very helpful in treating autoinflammatory diseases and have become the standard of care for treatment for some of these diseases. However, more research is needed on related diseases that may be treated with new and currently used IL-1 blocking agents.
- XOMA 052 is an experimental drug that is currently being tested as a possible treatment for type 2 diabetes. Initial studies have shown that XOMA 052 neutralizes a specific kind of IL-1, and is also active against certain indicators of inflammation. Researchers are interested in determining whether XOMA 052 can be used to treat autoinflammatory and related diseases.
- To determine the effectiveness of XOMA 052 as a treatment for inflammation in adults with the autoinflammatory diseases Familial Cold Autoinflammatory Syndrome (FCAS)/Muckle-Wells Syndrome (MWS) and Behcet's Disease.
- FCAS/ MWS: Individuals at least 18 years of age who have a known history of the typical disease.
- Behcet's Disease: Individuals at least 18 years of age who have evidence of active disease, such as oral or genital ulcers or eye disease.
- Participants will have an overnight evaluation of their disease, including optional tests (e.g., eye or skin exams). Participants who currently take medications to treat their symptoms will stop taking the medication and will be monitored by study researchers. At the first flare of symptoms, participants will begin to receive XOMA 052.
- Participants will have further tests on days 3, 7, and 10 after the initial dose of XOMA 052. If the disease remains under good control, participants will have a clinical exam every 5 days for up to 10 weeks until another disease flare occurs (determined either by symptoms or by inflammation observed in laboratory studies). If the disease is not well controlled with the initial dose of XOMA 052, participants will have additional doses starting at day 7 until either the disease is controlled or researchers determine that the medication is not effective.
- Participants will have the option to continue XOMA 052 treatments for up to 1 year. XOMA 052 wil...
Muckle Wells Syndrome
Drug: XOMA 052
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Pilot Study of XOMA 052 in Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle-Wells Syndrome (MWS) and Behcet's Disease (BD)|
- Changes in clinical and biochemical indicators of inflammation
- Duration of response to single dose
- Long term clinical and biochemical responses
- Number of flares during randomized withdrawal
- If applicable, assessment of the lack of complete response in relation to pharmacologic parameters.
|Study Start Date:||August 2010|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
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 the experimental drug candidate, XOMA 052 (XOMA (US), LLC) in the treatment of adult subjects with the autoinflammatory disorders familial cold autoinflammatory syndrome (FCAS) or Muckle-Wells Syndrome (MWS) associated with mutations in cryopyrin-encoding CIAS1 and in adult subjects with Behcet's Disease (BD), a disease which may be responsive to IL-1 blockade. XOMA 052 is a human recombinant IL-1beta antibody with picomolar affinity for IL-1beta and a beta half-life of 22.4 days in humans. This agent is currently in Phase 2 clinical studies for the treatment of Type 2 Diabetes and initial studies have shown activity against clinical and biochemical indicators of inflammation.
This pilot study is designed to address: 1) the utility of XOMA 052 in the treatment of FCAS / MWS, in a disease known to respond to IL-1 blockade (FCAS / MWS) as shown by a response to treatment with anakinra (Kineret(Registered Trademark), recombinant IL-1 receptor antagonist), rilonacept (Arcalyst(Registered Trademark), IL-1 Trap, a fusion protein of the IL-1 receptor and the Fc portion of IgG), and canakinumab (Ilaris(Registered Trademark), IL-1beta blocking antibody); the latter two FDA approved for the treatment of this condition; 2) the pharmacokinetics and dynamics of treatment with XOMA 052 in FCAS / MWS; 3) the effect of XOMA 052 on laboratory biomarkers in BD; and 4) an exploratory assessment of the utility of XOMA 052 in the treatment of BD.
For FCAS / MWS, biochemical and clinical correlates of autoinflammatory disease will be measured at baseline following withdrawal of currently used IL-1 inhibitors. Subjects will receive a course of therapy with XOMA 052 that is predicted to provide an estimated 4 weeks of anti-inflammatory activity. If a favorable response is obtained, the continuation phase will last twelve months. For BD, subjects will receive XOMA 052 for three to six months and patients with a positive response will then be randomized to withdrawal or continuation of drug for six months. Clinical and biochemical correlates of inflammation will be measured in both patient groups at appropriate intervals to assess response and to further elucidate disease mechanisms.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01211977
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|