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Active SystemicPhase 2SOJIANCT00570661

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

A Phase 2 study testing ITF2357 in people with Active Systemic and Onset Juvenile Idiopathic Arthritis, run by Italfarmaco at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 25 years
What is being tested?
ITF2357
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
5 sitesin 2 countries
Study dates
12 Sep 2006to 10 Jun 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Serbia3 sites

  • Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica

    Belgrade, Novi Belgrade, 6-811070

  • Institute of Rheumatology Belgrade Resavska

    Belgrade, 6911000

  • University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica

    Niš, Nis, 18000

Other trials in Serbia

Romania2 sites

  • Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni,

    Bucharest, 022328

  • Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district

    Bucharest, 041451

Other trials in Romania

About this study

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)

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
Read the 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.

Being tested
ITF2357

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ITF2357Drug

    Also called Givinostat, histone deacetylase inhibitor

    ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours.

Study groups in NCT00570661
Study groupRoleWhat they receive
ITF2357ExperimentalITF2357 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
Receives: Drug: ITF2357

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At week 12

Secondary outcomes (19)

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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.

  4. 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.

    Measured: 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.

  5. 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.

    Measured: 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.

  6. JIA Outcome Core Set Variables - ESR

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

    Measured: 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.

  7. 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.

    Measured: 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.

  8. 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).

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  9. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Typical SOJIA Rash

    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

    Typical SOJIA is a salmon pink rash on the trunk during the febrile episodes.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

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

    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

    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.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  11. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Hepatomegaly and/or Splenomegaly

    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

    Hepatomegaly and/or splenomegaly was scored as present if confirmed by ultrasound evaluation and established after comparison to age standards for organ size.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

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

    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

    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.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  13. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Erythrocyte Sedimentation Rate (ESR)

    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

    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%.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  14. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - C-reactive Protein (CRP)

    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

    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%.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  15. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - White Blood Cell (WBC)

    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

    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%.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  16. Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Haemoglobin (Hb)

    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

    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%.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

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

    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

    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%.

    Measured: Pre-treatment, Weeks 4, 8, 12, and 1-month follow up

  18. 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.

    Measured: At weeks 2, 4, 6, 8, 10 and 12.

  19. 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.

    Measured: At week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2007 (estimated)
  2. Study start12 Sep 2006
  3. Primary completion25 Aug 2008
  4. Study completion10 Jun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00570661
Sponsor's protocol ID
DSC/05/2357/19
Acronym
SOJIA
Status last verified
Apr 2021
First submitted
10 Dec 2007
Last updated
4 May 2021
Data monitoring committee
No

Publications

  • 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.

    PubMed 21538322

  • 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.

    PubMed 21308151

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ITF2357 in people with Active Systemic and Onset Juvenile Idiopathic Arthritis, run by Italfarmaco at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Serbia, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Completing Week 12 of Treatment (time frame: At week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00570661, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2021.

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