Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00442182 |
| Other study ID # |
2006/112 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
February 28, 2007 |
| Last updated |
February 28, 2007 |
| Start date |
September 2006 |
Study information
| Verified date |
February 2007 |
| Source |
Radboud University |
| Contact |
Evelien J Bodar, MD |
| Phone |
0031 24 3617276 |
| Email |
e.bodar[@]aig.umcn.nl |
| Is FDA regulated |
No |
| Health authority |
Italy: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
| Study type |
Interventional
|
Clinical Trial 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.
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.
