Clinical Trial: The Efficacy and Safety of ITF2357 in AIS
Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional
Official Title: The Effects and Side Effects of ITS2357 in Autoinflammatory Syndromes
Brief Summary: Autoinflammatory syndromes (AIS) are a group of disorders characterized by recurrent episodes of inflammation.Although for the hereditary autoinflammatory diseases the genetic mutations are known it remains largely unclear how these mutations lead to recurrent inflammatory attacks. Treatment of the inflammatory symptoms remains a challenge. With beneficial responses reported during treatment with simvastatin, etanercept or anakinra in some but not all patients. ITF2357 is an orally active histon deacetylase inhibitor with a potent anti-inflammatory effect due to inhibition of pro-inflammatory cytokines (IL-1β, TNFα, IFNg, IL-6). We expect that ITF2357 is able to modify the clinical symptoms of AIS patients and induce clinical complete remission or a reduction in attack duration.
Detailed Summary:
Rationale: Autoinflammatory syndromes (AIS) are a group of disorders characterized by recurrent episodes of inflammation. This occurs in the absence of autoantibodies and antigen specific T cells. To date 6 genetically distinct hereditary autoinflammatory syndromes are known and more recently other sporadic syndromes, such as the Schnitzler’s syndrome (urticaria, periodic fever and paraproteinemia) and Periodic Fever Aphtous stomatitis, Pharyngitis and Adenitis (PFAPA) are being recognized as AIS. Amyloidosis is a serious complication of chronic or recurrent inflammation seen in some of these syndromes. Although for the hereditary autoinflammatory diseases the genetic mutations are known it remains largely unclear how these mutations lead to recurrent inflammatory attacks. Symptomatic episodes are associated with increased serum concentrations of both pro-inflammatory mediators (TNFα, IL-6, IL1β and IFN-g) as well as of the anti-inflammatory compounds (IL-1ra, sTNFR p55 and sTNFR p75). In vitro and ex vivo experiments suggest a central role in the pathogenesis for IL-1β. The observation that rIL-1ra (anakinra) is highly effective in refractory TRAPS, CAPS, HIDS, refractory FMF and SS support this idea. Despite its effectiveness daily painful subcutaneous injections and injection site reactions remain a problem. ITF2357 is an orally active histon deacetylase inhibitor with a potent anti-inflammatory effect due to inhibition of pro-inflammatory cytokines (IL-1β, TNFα, IFNg, IL-6). We expect that ITF2357 is able to modify the clinical symptoms of AIS patients and induce clinical complete remission or a reduction in attack duration.
Objective: The primary objective is to asses whether ITF2357 is able to induce clinical complete remission in patients with continuous symptoms or reduce attack duration with > 33% in periodically symptomatic pati
Sponsor: Radboud University
Current Primary Outcome:
- clinical complete remission
- number of days of illness
Original Primary Outcome: Same as current
Current Secondary Outcome: side effects
Original Secondary Outcome: Same as current
Information By: Radboud University
Dates:
Date Received: February 28, 2007
Date Started: September 2006
Date Completion:
Last Updated: February 28, 2007
Last Verified: February 2007
