Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis
Condition: Active Systemic; Onset Juvenile Idiopathic Arthritis
MeSH terms: Arthritis; Arthritis, Juvenile
Intervention: ITF2357
Intervention description: ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours.
Intervention MeSH terms: Givinostat hydrochloride; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Not applicable. The study was open label.
Enrollment: 17.0
Sex: All
Minimum age: 2 Years
Maximum age: 25 Years
Healthy volunteers: No

Summary:

      This study has the following objectives:

      Primary objective:

      - To determine the safety and tolerability of oral ITF2357 in patients with active SOJIA with
      inadequate response or intolerance to standard therapy with oral steroids and methotrexate,
      with or without previously used biologic agents.

      Secondary objectives:

        -  to evaluate the effect of ITF2357 on disease activity in patients with active SOJIA

        -  to investigate the possibility of steroid dose tapering in patients with active SOJIA
           during ITF2357 treatment

        -  to assess the effect of ITF2357 on levels of circulating cytokines

        -  to assess the pharmacokinetic properties of ITF2357
    

Eligibility criteria:

        Inclusion Criteria:

          1. Established diagnosis of Systemic SOJIA according to ILAR criteria for at least six
             months before the study entry, with inadequate response or intolerance to standard
             therapy with oral steroids and/or methotrexate, with or without previously used
             biologic agents.

          2. Active disease for at least one month prior to enrolment as defined by the following
             criteria:

               -  Presence of arthritis plus at least one of the following:

                    -  Fever, defined as a body temperature >= 37,5 C degree at least once a day
                       during at least five consecutive days or presence of typical SOJIA
                       intermittent temperature chart

                    -  Rash, defined by presence of typical SOJIA salmon pink rash on the trunk and
                       elsewhere during the febrile episodes

                    -  Serositis (pericarditis, pleuritis, peritonitis) confirmed by ultrasound
                       and/or X-ray exploration or by presence of typical ECG findings in the case
                       of pericarditis

                    -  Lymphadenopathy, defined by lymph nodes enlargement to 1,5 cm or more
                       localized anywhere within the body, and/or hepatomegaly and/or splenomegaly,
                       confirmed by ultrasound evaluation and established after comparison to age
                       standards for organ size

                    -  ESR >= 20 mm/h (first hour) and/or CRP >= 10 mg/L. in the absence of
                       arthritis, two definite or one definite and one probable diagnostic criteria
                       plus ESR >=20 mm/h (first hour) and/or CRP >=10 mg/L

          3. Age at enrolment between 2 and 25 years

          4. Age at first SOJIA diagnosis < 16 years

          5. Previously introduced standard treatment of disease with steroids without satisfactory
             effect and concomitant treatment with oral steroids at a dose equivalent to >= 0,2
             mg/kg/day of prednisolone, unmodified for at least four weeks before patient's
             enrolment

          6. In case of concomitant methotrexate treatment, it has to be on stable dose >= 10mg/m2
             weekly for al least 4 weeks before pt enrollment

          7. Previous treatment with biologics, if any, during at least three months without
             satisfactory effect or with drug intolerability, discontinued for at least the period
             specified below before patient's enrolment:

               -  Two months for etanercept

               -  Six months for infliximab

          8. Other disease-modifying anti-rheumatic drugs possibly previously introduced have to be
             discontinued for a period of at least five half lives

          9. Concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at
             least four weeks before patient's enrolment

         10. Female of childbearing potential, using safe contraceptive measures

         11. Signed written informed consent before starting any study procedure

        Exclusion Criteria:

          1. Ongoing clinical relevant viral infection (eg.: Herpes Zoster, Ebstein barr, CMV,
             Systemic fungal infections or history of recurrent serious bacterial infection)

          2. History of macrophage activation syndrome

          3. Clinically significant illness i.e. any condition (including laboratory abnormalities)
             that in the opinion of the Investigator places the patient to unacceptable risk for
             adverse outcome if he/she were to participate in the study

          4. Psychiatric illness/social situations that would limit compliance with study
             medication and protocol requirements

          5. Congenital heart and/or central nervous system disorders

          6. Inherited metabolic diseases

          7. Positive serological testing for anti HCV, anti HIV and HBsAg (to be performed at
             screening)

          8. Pregnant or lactating women

          9. Presence of malignancy

         10. Any previous evidence, irrespective of its severity, of coronary disease, cardiac
             rhythm abnormalities or congestive heart failure

         11. QTc interval > 450 msec at screening evaluation

         12. Serum magnesium and potassium below the LLN at screening

         13. Unavoidable concomitant treatment with any drug known for potential risk of causing
             Torsades de Pointes