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

Primary Purpose

Active Systemic, Onset Juvenile Idiopathic Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ITF2357
Sponsored by
Italfarmaco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Active Systemic

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni,
  • Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district
  • University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica
  • Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica
  • Institute of Rheumatology Belgrade Resavska

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ITF2357

Arm Description

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 (dose strengths of 7.5, 10, 12.5, 15, 20 mg and 50 mg). Treatment was further prolonged up to 12 weeks in total if so suggested by the observed benefits and the lack of treatment-limiting toxicity

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
JIA Outcome Core Set Variables - ESR
Measurements of erythrocyte sedimentation rate (ESR) were performed at the local laboratory cooperating with each study site.
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.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Temperature
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin 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).
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Typical SOJIA Rash
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Typical SOJIA is a salmon pink rash on the trunk during the febrile episodes.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Lymphadenopathy
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Lymphadenopathy was scored as present or not present according to the following criterion: lymph node (nodes) enlargement to 1.5 cm or more, localized anywhere within the body.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Hepatomegaly and/or Splenomegaly
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Hepatomegaly and/or splenomegaly was scored as present if confirmed by ultrasound evaluation and established after comparison to age standards for organ size.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Serositis
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Serositis (pericarditis, pleuritis or peritonitis) was scored as present if confirmed by ultrasound and/or X-ray exploration or by the presence of typical ECG findings in the case of pericarditis.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Erythrocyte Sedimentation Rate (ESR)
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit ESR was scored as present or not present according to the following criterion: ESR considered as elevated if ≥ 20 mm/h (first hour) At the subsequent visits ESR was scored 0 (Not present) if decreased by at least 30% as compared to pre-treatment value or normalized (< 20 mm/h); score 1 (Present) if increased or decreased less than 30%.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - C-reactive Protein (CRP)
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit CRP was scored as present or not present according to the following criterion: CRP considered as elevated if ≥ 10 mg/L. At the subsequent visits CRP was scored 0 (Not present) if decreased by at least 30% compared to pre-treatment value or normalized (< 10 mg/L); score 1 (Present) if increased or decreased less than 30%.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - White Blood Cell (WBC)
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit WBC was scored as present or not present according to the following criterion: Leukocyte count considered as elevated if ≥ 12 x 103/μL. At the subsequent visits WBC was scored 0 (Not present) if decreased by 20% compared to pre-treatment value or normalized (< 12x103/μL); score 1 (Present) if increased or decreased less than 20%.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Haemoglobin (Hb)
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit Hb was scored as present or not present according to the following criterion: Haemoglobin considered as lowered if below 11g/dL. At the subsequent visits Hb was scored 0 (Not present) if increased by 20% compared to pre-treatment value or normalized (> 11 g/dL); score 1 (Present) if decreased or increased less than 20%.
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Thrombocytes
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit thrombocyte count was scored as present or not present according to the following criterion: Thrombocyte count considered as increased if ≥ 400x103/μL. At the subsequent visits thrombocyte count was scored 0 (Not present) if decreased by 20% compared to pretreatment value or normalized (< 400x103/μL); score 1 (Present) if increased or decreased less than 20%.
Number of Patients With JIA Plus SFS Clinical Improvement
Clinical improvement at week 2, 4, 6, 8, 10 and 12 was evaluated on the basis of JIA30, JIA50 and JIA70 plus SFS (two points decrease in SFS) as per protocol. Patients were considered as improved and with positive therapeutic response if 3 or more JIA Core Set Variables improved by 30% and no more than one worsened by 30%. JIA50 and JIA70 were defined as an improvement of 3 or more JIA Core Set Variables by 50% and 70%, respectively, and no more than 1 worsened by 30%. Additionally two points decrease in Systemic Feature Score were considered as disease improvement.
Number of Patients With Sufficient Therapeutic Response at Week 4 to Continue Treatment
Therapeutic response at week 4 was considered sufficient by the Investigator if a decrease in Systemic Feature Score of 2 (at least one of the first five variables) and/or JIA30 response (or above: 50 or 70) was obtained.

Full Information

First Posted
December 10, 2007
Last Updated
April 8, 2021
Sponsor
Italfarmaco
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1. Study Identification

Unique Protocol Identification Number
NCT00570661
Brief Title
Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis
Acronym
SOJIA
Official Title
Phase II, Open Label, International, Multicentre Clinical Trial to Investigate Safety and Efficacy of Oral ITF2357 in Patients With Active Systemic Onset Juvenile Idiopathic Arthritis (SOJIA)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
September 12, 2006 (Actual)
Primary Completion Date
August 25, 2008 (Actual)
Study Completion Date
June 10, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Italfarmaco

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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
Detailed Description
The present study has been designed in order to evaluate safety and tolerability of 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, and to have a preliminary evaluation of efficacy of ITF2357 in the treatment of SOJIA. ITF2357 will be administered orally at the daily cumulative dose of 1.5 mg/kg: this dose in children/young adults is considered roughly equivalent to the dose of 1 mg/kg/day in adults, which so far has been proven to be free of any relevant safety concerns both in healthy volunteers and in patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Active Systemic, Onset Juvenile Idiopathic Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Not applicable. The study was open label.
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ITF2357
Arm Type
Experimental
Arm Description
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 (dose strengths of 7.5, 10, 12.5, 15, 20 mg and 50 mg). Treatment was further prolonged up to 12 weeks in total if so suggested by the observed benefits and the lack of treatment-limiting toxicity
Intervention Type
Drug
Intervention Name(s)
ITF2357
Other Intervention Name(s)
Givinostat, histone deacetylase inhibitor
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.
Primary Outcome Measure Information:
Title
Number of Patients Completing Week 12 of Treatment
Description
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 Outcome Measure Information:
Title
JIA Outcome Core Set Variables - Patient Global Assessment
Description
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.
Title
JIA Outcome Core Set Variables - Physician Global Assessment
Description
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.
Title
JIA Outcome Core Set Variables - Number of Joints With Active Arthritis
Description
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.
Title
JIA Outcome Core Set Variables - Number of Joints With Limitation
Description
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.
Title
JIA Outcome Core Set Variables - CHAQ
Description
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.
Title
JIA Outcome Core Set Variables - ESR
Description
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.
Title
Overall SFS Results - Sum of First Five Variables and Sum of Last Five Variables
Description
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.
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Temperature
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin 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).
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Typical SOJIA Rash
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Typical SOJIA is a salmon pink rash on the trunk during the febrile episodes.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Lymphadenopathy
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Lymphadenopathy was scored as present or not present according to the following criterion: lymph node (nodes) enlargement to 1.5 cm or more, localized anywhere within the body.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Hepatomegaly and/or Splenomegaly
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Hepatomegaly and/or splenomegaly was scored as present if confirmed by ultrasound evaluation and established after comparison to age standards for organ size.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Serositis
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count Serositis (pericarditis, pleuritis or peritonitis) was scored as present if confirmed by ultrasound and/or X-ray exploration or by the presence of typical ECG findings in the case of pericarditis.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Erythrocyte Sedimentation Rate (ESR)
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit ESR was scored as present or not present according to the following criterion: ESR considered as elevated if ≥ 20 mm/h (first hour) At the subsequent visits ESR was scored 0 (Not present) if decreased by at least 30% as compared to pre-treatment value or normalized (< 20 mm/h); score 1 (Present) if increased or decreased less than 30%.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - C-reactive Protein (CRP)
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit CRP was scored as present or not present according to the following criterion: CRP considered as elevated if ≥ 10 mg/L. At the subsequent visits CRP was scored 0 (Not present) if decreased by at least 30% compared to pre-treatment value or normalized (< 10 mg/L); score 1 (Present) if increased or decreased less than 30%.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - White Blood Cell (WBC)
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit WBC was scored as present or not present according to the following criterion: Leukocyte count considered as elevated if ≥ 12 x 103/μL. At the subsequent visits WBC was scored 0 (Not present) if decreased by 20% compared to pre-treatment value or normalized (< 12x103/μL); score 1 (Present) if increased or decreased less than 20%.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Haemoglobin (Hb)
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit Hb was scored as present or not present according to the following criterion: Haemoglobin considered as lowered if below 11g/dL. At the subsequent visits Hb was scored 0 (Not present) if increased by 20% compared to pre-treatment value or normalized (> 11 g/dL); score 1 (Present) if decreased or increased less than 20%.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Thrombocytes
Description
SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit thrombocyte count was scored as present or not present according to the following criterion: Thrombocyte count considered as increased if ≥ 400x103/μL. At the subsequent visits thrombocyte count was scored 0 (Not present) if decreased by 20% compared to pretreatment value or normalized (< 400x103/μL); score 1 (Present) if increased or decreased less than 20%.
Time Frame
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up
Title
Number of Patients With JIA Plus SFS Clinical Improvement
Description
Clinical improvement at week 2, 4, 6, 8, 10 and 12 was evaluated on the basis of JIA30, JIA50 and JIA70 plus SFS (two points decrease in SFS) as per protocol. Patients were considered as improved and with positive therapeutic response if 3 or more JIA Core Set Variables improved by 30% and no more than one worsened by 30%. JIA50 and JIA70 were defined as an improvement of 3 or more JIA Core Set Variables by 50% and 70%, respectively, and no more than 1 worsened by 30%. Additionally two points decrease in Systemic Feature Score were considered as disease improvement.
Time Frame
At weeks 2, 4, 6, 8, 10 and 12.
Title
Number of Patients With Sufficient Therapeutic Response at Week 4 to Continue Treatment
Description
Therapeutic response at week 4 was considered sufficient by the Investigator if a decrease in Systemic Feature Score of 2 (at least one of the first five variables) and/or JIA30 response (or above: 50 or 70) was obtained.
Time Frame
At week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 < 16 years 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nemanja Damjanov, MD, PhD
Organizational Affiliation
Institute of Rheumatology Belgrade
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni,
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district
City
Bucharest
ZIP/Postal Code
041451
Country
Romania
Facility Name
University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica
City
Niš
State/Province
Nis
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica
City
Belgrade
State/Province
Novi Belgrade
ZIP/Postal Code
6-811070
Country
Serbia
Facility Name
Institute of Rheumatology Belgrade Resavska
City
Belgrade
ZIP/Postal Code
6911000
Country
Serbia

12. IPD Sharing Statement

Citations:
PubMed Identifier
21538322
Citation
Vojinovic J, Damjanov N, D'Urzo C, Furlan A, Susic G, Pasic S, Iagaru N, Stefan M, Dinarello CA. Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2011 May;63(5):1452-8. doi: 10.1002/art.30238.
Results Reference
derived
PubMed Identifier
21308151
Citation
Vojinovic J, Damjanov N. HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol Med. 2011 May-Jun;17(5-6):397-403. doi: 10.2119/molmed.2011.00030. Epub 2011 Feb 4.
Results Reference
derived

Learn more about this trial

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

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