Interleukin-1 Trap to Treat Autoinflammatory Diseases

Completed · Phase 2

Conditions studied: Inflammation, Familial Mediterranean Fever, Still's Disease, Adult-Onset

In brief

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, IL 1 Trap (Regeneron Pharmaceuticals, Inc.) in the treatment of adult subjects with the autoinflammatory disorders Neonatal Onset Multisystem Inflammatory Disease (NOMID), Muckle-Wells Syndrome (MWS), and Familial Cold Autoinflammatory Syndrome (FCAS), Familial Mediterranean Fever (FMF), and adult Still's disease. FMF is associated with mutations in pyrin encoding MEFV. NOMID, MWS and FCAS are associated with mutations in cryopyrin-encoding CIAS1. This pilot study is designed to address: 1) the utility of IL 1 Trap in the treatment of subjects with diseases known to respond to IL-1 blockade (NOMID/MWS/FCAS) as shown by response to treatment with anakinra \[Kineret\]; 2) the response to IL-1 blockade of subjects with Adult Still's disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has been established in NOMID/MWS/FCAS subjects; and 3) the biochemistry and genetics of autoinflammatory diseases and IL-1 related inflammation. IL-1 Trap is a recombinant fusion protein with picomolar affinity for IL-1 and a half-life of approximately 7.5 days in humans. This agent is currently in Phase 2 clinical studies for the treatment of rheumatoid arthritis and initial studies have shown activity against clinical and biochemical indicators of inflammation. Compared with anakinra, this agent may exhibit improved dosing convenience, potential for fewer injection site reactions, and improved efficacy due to the extremely high affinity of IL-1Trap for its target. In this study, biochemical, genetic, and clinical correlates of autoinflammatory disease will initially be measured at baseline following a withdrawal of any TNF or IL-1 inhibitor medications where applicable. Subjects will receive a course of therapy with IL-1 Trap that is predicted to provide an estimated 3-4 weeks of anti-inflammatory activity. Clinical, biochemical, and genetic correlates of inflammation will be measured at appropriate intervals to ascertain response and to further elucidate disease mechanisms. Subjects will be eligible, based on clinical response, to enter a 1- year extension phase with IL-1 Trap. Those subjects who complete the 1-year extension phase, and maintain improved clinical and laboratory parameters compared to baseline values, may continue to receive study medication at their current dose until the study drug is commercially available. Investigator comment: This protocol (from the NIH standpoint) is a continuation of the ongoing protocol 05-AR-0014, with a new change in study sponsor, the NIH replacing Regeneron as sponsor. this protocol therefore still contains background and procedural information that refer to patients with FMF and FCAS and or MWS and Still's disease, however only patients with Still's disease will be newly enrolled from this point on, enrollment for the FCAS and or MWS patients has already been completed and it has been decided to not enroll any more FMF patients because the number of subjects is too low to reach reasonable conclusions, in addition it has been difficult to recruit patients that are eligible. The background section and study procedures have largely been left as in the currently IRB approved protocol.

Key facts

Study ID: NCT00094900
Run by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
People needed: 11
Starts: 2004-10-01
Expected to finish: 2010-12-01
Last updated by the study team: 2014-03-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Treatment with a live virus vaccine during 3 months prior to baseline visit. No live vaccines will be allowed throughout the course of this study.
Current treatment with TNF inhibitors or recent discontinuation of TNF inhibitors (use within less than 5 half-lives of TNF inhibitor agent).
Presence of active infections or a history of pulmonary TB infection with or without documented adequate therapy. Subjects with current active TB, or recent close exposure to an individual with active TB are excluded from the study.
Chest x-ray read by a radiologist with pleural scarring and/or calcified granuloma consistent with prior TB.
Positive test for or prior history of HIV, Hepatitis B or C.
History or concomitant diagnosis of congestive heart failure.
History of malignancy. Subjects deemed cured of superficial malignancies such as cutaneous basal or squamous cell carcinomas, or in situ cervical cancer may be enrolled.
Known hypersensitivity to CHO cell derived biologicals or any components of IL 1 Trap.
Presence of any additional rheumatic disease or significant systemic disease. For example, major chronic infectious/ inflammatory/ immunologic disease (such as inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, SLE in addition to autoinflammatory disease).
Presence of any of the following laboratory abnormalities at enrollment visit: creatinine greater than 1.5 times the upper limit of normal, WBC less than 3.6 x 10(9)/mm(3); platelet count less than 150,000 mm(3); ALT or AST greater than 2.0 x ULN (ALT/AST greater than 2.0 x ULN in an adult Still's disease patient would prompt a hepatology consult prior to enrollment unless these abnormalities are considered by the Principal Investigator to be reflective of the underlying Still's disease).
Lactating females or pregnant females.
Subjects with asthma not adequately controlled on current therapy.
Enrollment in any other investigational treatment study or use of an investigational agent, or has not yet completed at least 4 weeks or 5 half-lives, whichever is longer, since ending another investigational device or drug trial.
Subjects for whom there is concern about compliance with the protocol procedures.
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 inappropriate for entry into this study.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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