NCT00570661 - Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis | Crick

Eligibility

Sex: ALLMin age: 2 YearsMax age: 25 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Patients Completing Week 12 of Treatment

The primary endpoint describes the number of patients who has completed week 12 of treatment with ITF2357, both in the Per protocol (PP) population and in the Intention to treat (ITT) population. ITF2357 hard gelatine capsules were administered orally, in fed conditions, at the cumulative daily dose of 1.5 mg/kg achieved by administration of 0.75 mg/kg at 12-hour interval for 4 weeks initially. The doses of 1.5 mg/kg/day were achieved by administration of an appropriate number of capsules of definite strength. Treatment was further prolonged up to 12 weeks in total if so suggested by the observed benefits and the lack of treatment-limiting toxicity.

Time frame: At week 12

Secondary Outcomes

JIA Outcome Core Set Variables - Patient Global Assessment

Patient/parent global Visual Analogue Scale (VAS) is from 0 to 100. The lower the score, the better the outcome.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

JIA Outcome Core Set Variables - Physician Global Assessment

Physician global Visual Analogue Scale (VAS) is from 0 to 100. The lower the score, the better the outcome.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

JIA Outcome Core Set Variables - Number of Joints With Active Arthritis

Number of active joints is from 0 to 75. The lower the score, the better the outcome.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

JIA Outcome Core Set Variables - Number of Joints With Limitation

Number of joints with limited range of motion is from 0 to 75. The lower the score, the better the outcome.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

JIA Outcome Core Set Variables - CHAQ

The Childhood Health Assessment Questionnaire (CHAQ) is from 0 to 3. For each of 8 section (Dressing and care, Getting up, Eating, Walking, Hygiene, Grasping, Catching, Activities) answers patient is getting 0,1,2 or 3 points (no difficulties, some difficulties, much difficulties, unable to do, respectively). The sum of points is then divided by 8 to get score 0 - 3. The lower the score, the better the outcome.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

JIA Outcome Core Set Variables - ESR

Measurements of erythrocyte sedimentation rate (ESR) were performed at the local laboratory cooperating with each study site.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

Overall SFS Results - Sum of First Five Variables and Sum of Last Five Variables

Modified Systemic Feature Score (SFS) variables included: * temperature, rash, lymph nodes, liver and spleen size, and clinical evidence of serositis (clinical variables) * ESR, CRP, leukocyte count, haemoglobin, thrombocyte count (laboratory variables). Items in both sets of variables were scored as present (1) or not present (0) based on predefined criteria. SFS data were presented as the sum of the first 5 items and the sum of the last 5 items. Each sum could range from a minimum of 0 to a maximum of 5.

Time frame: At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month follow-up (FU1) in the PP and ITT populations respectively.

Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Temperature

SFS variables included: 1. temperature 2. rash 3. lymph nodes 4. liver and spleen size 5. clinical evidence of serositis (pericarditis, pleuritis or peritonitis) 6. ESR 7. CRP 8. leukocyte count 9. haemoglobin 10. thrombocyte count Temperature was scored as present or not present according to the following criterion: body temperature ≥ 37.5 °C at least once a day during at least five consecutive days or presence of typical SOJIA intermittent temperature chart (patients' temperature chart analysis).