Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis

Inclusion Criteria:

• patients of both genders, aged 2 to 17 years, with established diagnosis of polyarticular course Juvenile Idiopathic Arthritis (see before for specific subtypes) according to ILAR criteria (Petty RE et al., 2004) for at least six months before the study entry
• age at polyarticular JIA diagnosis < 16 years
• active disease for at least 6 months prior to enrolment as defined by the following criteria:
• presence of at least 5 active joints (those with swelling or, in the absence of swelling, limited range of motion accompanied by pain/tenderness)
• inadequate response to, or intolerance to, at least one biologic agent such as, but not limited to, etanercept, infliximab, and adalimumab.
• maximum allowed steroid dose 0.2 mg/kg/day or 10 mg/day (whichever is lower) of prednisone or equivalent
• in case of concomitant methotrexate treatment, it has to be on a stable dose ≤15 mg/m2 weekly for at least 1 month before patient's enrolment
• 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

Exclusion Criteria:

• patient with fever related to JIA or other systemic features of JIA during 12 months before entering the study
• active bacterial or mycotic infection requiring antimicrobial treatment
• episode of macrophage activation syndrome in the last 6 months
• a baseline prolongation of QT/QTc interval, use of concomitant medications that prolong the QT/QTc interval or history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) (Appendix C)
• clinically significant cardiovascular disease
• 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
• inherited metabolic diseases
• presence of malignancy
• pregnancy or lactation
• positive blood test for HIV
• active EBV infection, active B and/or C hepatitis
• platelet count <100x109/L
• absolute neutrophil count <1.5x109/L
• serum creatinine >2xULN.
• total serum bilirubin >1.5xULN.
• serum AST/ALT > 3xULN.
• congenital heart and/or central nervous system disorders