Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00442182
Status:
UNKNOWN
Last Update Posted:
2007-03-01
First Post:
2007-02-28
Brief Title:
The Efficacy and Safety of ITF2357 in AIS
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
The Effects and Side Effects of ITS2357 in Autoinflammatory Syndromes
Status:
UNKNOWN
Status Verified Date:
2007-02
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Autoinflammatory syndromes AIS are a group of disorders characterized by recurrent episodes of inflammationAlthough 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 Description:
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 Schnitzlers 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 patients Secondary objectives are the emergence of adverse events and toxicity as well as the influence of ITF2357 on cytokine production and laboratory parameters for infection and metabolism
Study design Open Label Pilot Study Study population AIS patients 18 years or older with severe disease
Intervention Patients with continuous symptoms will receive 2-3 times a day 50mg capsule ITF2357 for a total period of 90 days Patients with periodic symptoms will take ITF2357 2-3 times a day 50mg on 7-14 consecutive days during 6-12 attacks
Main study parameters A clinical complete remission will be regarded as a clinical score CS 10 scored on the symptom score list in the absence of a temperature 380C and normalisation of CRP and WBC levels The end of an attack will be defined as a CS 20 in the absence of a temperature 380C
Nature and extent of the burden and risks associated with participation benefit and group relatedness All patients will be admitted once at the beginning of the study for 3 days in this period there will be performed a daily venipuncture a history and physical examination twice and an ECG once They will visit the outpatient clinic four times for physical examination history venipuncture and an ECG Patients are asked to complete a symptom score list on which they can note down the date number of ITF2357 capsules taken and if present co-medication symptoms temperature and adverse events Patients are asked to collect a portion of morning urine once a week ITF2357 showed the following adverse reactions asymptomatic trombocytopenia and perhaps increased incidence of mild infections mainly of the upper respiratory tract There were gastrointestinal complaints in the sense of nausea vomiting abdominal pain and diarrhea
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 patients Secondary objectives are the emergence of adverse events and toxicity as well as the influence of ITF2357 on cytokine production and laboratory parameters for infection and metabolism
Study design Open Label Pilot Study Study population AIS patients 18 years or older with severe disease
Intervention Patients with continuous symptoms will receive 2-3 times a day 50mg capsule ITF2357 for a total period of 90 days Patients with periodic symptoms will take ITF2357 2-3 times a day 50mg on 7-14 consecutive days during 6-12 attacks
Main study parameters A clinical complete remission will be regarded as a clinical score CS 10 scored on the symptom score list in the absence of a temperature 380C and normalisation of CRP and WBC levels The end of an attack will be defined as a CS 20 in the absence of a temperature 380C
Nature and extent of the burden and risks associated with participation benefit and group relatedness All patients will be admitted once at the beginning of the study for 3 days in this period there will be performed a daily venipuncture a history and physical examination twice and an ECG once They will visit the outpatient clinic four times for physical examination history venipuncture and an ECG Patients are asked to complete a symptom score list on which they can note down the date number of ITF2357 capsules taken and if present co-medication symptoms temperature and adverse events Patients are asked to collect a portion of morning urine once a week ITF2357 showed the following adverse reactions asymptomatic trombocytopenia and perhaps increased incidence of mild infections mainly of the upper respiratory tract There were gastrointestinal complaints in the sense of nausea vomiting abdominal pain and diarrhea
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None