At a glance
ClinicalIndex Comparison Record- ✓Adult (≥18 years) with inflammatory disease and prior participation in NIH study 94-AR-0105
- ✓Active disease in NOMID, MWS, FCAS, FMF, or adult Still's disease based on clinical signs/symptoms and/or biochemical markers (CRP, SAA, ESR)
- ✓FMF requires positive MEFV mutation test and inadequate response to colchicine (≤2 mg/day) with ≥1 flare/month or acute phase reactants ≥1.5× ULN despite maximum tolerated colchicine dose
- ✓Stable dose of steroids, NSAIDs, DMARDs, or colchicine for 4 weeks prior to enrollment
- ✕Active infection or history of pulmonary TB with or without adequate therapy, or current/recent close exposure to active TB
- ✕Chest X-ray with pleural scarring and/or calcified granuloma consistent with prior TB
- ✕Current or recent TNF inhibitor use (within <5 half-lives of the agent)
- ✕Live virus vaccine within 3 months before baseline or during study
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Continuation of a Pilot Open-Label Study of IL 1 Trap in Adult Subjects With Autoinflammatory Diseases: A Therapeutic Approach to Study Pathogenesis
In Brief
A Phase 2 clinical trial evaluating IL-1 Trap for Inflammation and 2 related conditions. Completed, enrolled 11 participants across 1 site.
Detailed Summary
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.