The Efficacy and Safety of ITF2357 in AIS
Primary Purpose
Autoinflammatory Syndromes, HIDS, TRAPS
Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
ITF2357
Sponsored by
About this trial
This is an interventional treatment trial for Autoinflammatory Syndromes focused on measuring autoinflammatory syndromes
Eligibility Criteria
Inclusion Criteria:
- Autoinflammatory syndrome (hereditary or acquired)
- Age ³18 years
- Severe active disease (≥1 attack every eight weeks or continuous symptoms).
An attack will be defined as:
- Temperature of ≥38 ºC not otherwise explained.
- At least two other accompanying symptoms (e.g. joint pain, lymphadenopathy, skin lesions, abdominal symptoms)
- written informed consent obtained
Exclusion Criteria:
- Age < 18 years
- Pregnancy and lactation
- Increased risk for infection or current infection
- Renal failure (GFR<30ml/1.73m2/min)
- Pre-existing malignancy
Sites / Locations
- Radboud University Medical Centre NijmegenRecruiting
Outcomes
Primary Outcome Measures
clinical complete remission
number of days of illness
Secondary Outcome Measures
side effects
Full Information
NCT ID
NCT00442182
First Posted
February 28, 2007
Last Updated
February 28, 2007
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00442182
Brief Title
The Efficacy and Safety of ITF2357 in AIS
Official Title
The Effects and Side Effects of ITS2357 in Autoinflammatory Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2007
Overall Recruitment Status
Unknown status
Study Start Date
September 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Radboud University Medical Center
4. Oversight
5. Study Description
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 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 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 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 > 38.0°C 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 > 38.0°C.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoinflammatory Syndromes, HIDS, TRAPS, Schnitzler's Syndrome
Keywords
autoinflammatory syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
ITF2357
Primary Outcome Measure Information:
Title
clinical complete remission
Title
number of days of illness
Secondary Outcome Measure Information:
Title
side effects
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Autoinflammatory syndrome (hereditary or acquired)
Age ³18 years
Severe active disease (≥1 attack every eight weeks or continuous symptoms).
An attack will be defined as:
Temperature of ≥38 ºC not otherwise explained.
At least two other accompanying symptoms (e.g. joint pain, lymphadenopathy, skin lesions, abdominal symptoms)
written informed consent obtained
Exclusion Criteria:
Age < 18 years
Pregnancy and lactation
Increased risk for infection or current infection
Renal failure (GFR<30ml/1.73m2/min)
Pre-existing malignancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Evelien J Bodar, MD
Phone
0031 24 3617276
Email
e.bodar@aig.umcn.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Jos WM van der Meer, MD PhD
Phone
0031 24 3618819
Email
j.vandermeer@aig.umcn.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jos WM van der Meer, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Medical Centre Nijmegen
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Evelien J Bodar, MD
12. IPD Sharing Statement
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The Efficacy and Safety of ITF2357 in AIS
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