Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis

Inclusion Criteria

• 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.
• 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
• Age at enrolment between 2 and 25 years
• Age at first SOJIA diagnosis = 0,2 mg/kg/day of prednisolone, unmodified for at least four weeks before patient's enrolment
• In case of concomitant methotrexate treatment, it has to be on stable dose >= 10mg/m2 weekly for al least 4 weeks before pt enrollment
• 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
• Other disease-modifying anti-rheumatic drugs possibly previously introduced have to be discontinued for a period of at least five half lives
• Concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at least four weeks before patient's enrolment
• Female of childbearing potential, using safe contraceptive measures
• Signed written informed consent before starting any study procedure

Exclusion Criteria

• Ongoing clinical relevant viral infection (eg.: Herpes Zoster, Ebstein barr, CMV, Systemic fungal infections or history of recurrent serious bacterial infection)
• History of macrophage activation syndrome
• 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
• Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
• Congenital heart and/or central nervous system disorders
• Inherited metabolic diseases
• Positive serological testing for anti HCV, anti HIV and HBsAg (to be performed at screening)
• Pregnant or lactating women
• Presence of malignancy
• Any previous evidence, irrespective of its severity, of coronary disease, cardiac rhythm abnormalities or congestive heart failure
• QTc interval > 450 msec at screening evaluation
• Serum magnesium and potassium below the LLN at screening
• Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes