A multicenter, open label, dose finding study to evaluate efficacy and safety of Givinostat administered in two different doses in patients with polyarticular course Juvenile Idiopathic Arthritis (poly JIA) not adequately responding to the standard treatment

Phase 1

• Conditions: Polyarticular course Juvenile Idiopathic Arthritis (poly JIA); MedDRA version: 12.1Level: LLTClassification code 10059176Term: Juvenile idiopathic arthritis

• Registration Number: EUCTR2010-019094-15-BE
• Lead Sponsor: Italfarmaco S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-20
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. patients of both genders, aged 2 to less than 18 years, with established diagnosis of polyarticular course Juvenile Idiopathic Arthritis (see before for specific subtypes) according to ILAR criteria for at least six months before the study entry
2. age at polyarticular JIA diagnosis < 16 years
3. 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, in?iximab, and adalimumab
4. maximum allowed steroid dose 0.2 mg/kg/day or 10 mg/day (whichever is lower) of prednisone or equivalent
5. 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
6. previous treatment with biologics, if any, discontinued for an adequate wash-out period, depending on the specific drug
7. other disease-modifying anti-rheumatic drugs possibly previously introduced have to be discontinued for a period of at least five half-lives
8. concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at least four weeks before patient’s enrolment

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. patient with fever related to JIA or other systemic features of JIA during 12 months before entering the study
2. active bacterial or mycotic infection requiring antimicrobial treatment
3. episode of macrophage activation syndrome in the last 6 months
4. 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)
5. clinically significant cardiovascular disease
6. 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
7. psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
8. inherited metabolic diseases
9. presence of malignancy
10. pregnancy or lactation
11. positive blood test for HIV
12. active EBV infection, active B and/or C hepatitis
13. platelet count <100x109/L
14. absolute neutrophil count <1.5x109/L
15. serum creatinine >2xULN.
16. total serum bilirubin >1.5xULN.
17. serum AST/ALT > 3xULN.
18. congenital heart and/or central nervous system disorders

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of Givinostat administered in two different doses to patients with polyarticular course JIA not adequately responding to the standard treatment, to the purpose of selecting the best dose to be tested on a larger scale in a following phase III clinical trial. ;Secondary Objective: -;Primary end point(s): Proportion of patients achieving an ACR pediatric 30 level of response after 12 weeks (day 85) of treatment.