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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ITF2357 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ITF2357 | Drug | ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
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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:
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Nemanja Damjanov, MD, PhD | Institute of Rheumatology Belgrade | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni, | Bucharest | 022328 | Romania | |||
| Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21538322 | Derived | 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. | |
| 21308151 | Derived | 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. |
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Patients with SOJIA according to the International League against Rheumatism criteria, established before the age of 16 y and for at least 6 mo before the study entry, having active disease for at least 1 mo while receiving more than 0.2 mg/kg/day prednisolone or equivalent steroid with/without concurrent methotrexate therapy (≥ 10 mg/m2 weekly).
Seventeen patients were screened and enrolled in the study
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| ID | Title | Description |
|---|---|---|
| FG000 | ITF2357 | 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 ITF2357: ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population: all recruited patients who received at least one dose of the study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | ITF2357 | 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 ITF2357: ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. | Posted | Count of Participants | Participants | At week 12 |
|
At weeks 1, 2, 4, 6, 8, 10, 12 (end of treatment) and FU1 and FU3
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IT2357 - Safety Population | Safety population: all recruited patients who received at least one dose of the study medication. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Varicella | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injury | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maurizio Caserini, MD | Italfarmaco SpA | +39 0264431 | m.caserini@italfarmaco.com |
| ID | Term |
|---|---|
| C502418 | givinostat hydrochloride |
| C575255 | givinostat |
| D056572 | Histone Deacetylase Inhibitors |
| ID | Term |
|---|---|
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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Not applicable. The study was open label.
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|
| 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. |
| 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. | 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. | 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. | 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. | 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:
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. | 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:
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). | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Typical SOJIA Rash | SFS variables included:
Typical SOJIA is a salmon pink rash on the trunk during the febrile episodes. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Lymphadenopathy | SFS variables included:
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. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Hepatomegaly and/or Splenomegaly | SFS variables included:
Hepatomegaly and/or splenomegaly was scored as present if confirmed by ultrasound evaluation and established after comparison to age standards for organ size. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Serositis | SFS variables included:
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. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Erythrocyte Sedimentation Rate (ESR) | SFS variables included:
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%. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - C-reactive Protein (CRP) | SFS variables included:
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%. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - White Blood Cell (WBC) | SFS variables included:
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%. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Haemoglobin (Hb) | SFS variables included:
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%. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Thrombocytes | SFS variables included:
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%. | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
| 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. | At weeks 2, 4, 6, 8, 10 and 12. |
| 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. | At week 4 |
| Bucharest |
| 041451 |
| Romania |
| University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica | Niš | Nis | 18000 | Serbia |
| Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica | Belgrade | Novi Belgrade | 6-811070 | Serbia |
| Institute of Rheumatology Belgrade Resavska | Belgrade | 6911000 | Serbia |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 |
| ITF2357 - PP Population |
All patients in the study PP population (N=9) completed 12 weeks of treatment with ITF2357 according to the specifications of the protocol and thus reached the primary end-point of the study. |
| OG001 | ITF2357 - ITT Population | The analysis was repeated on the ITT population: 10 out of the 17 patients in the ITT population completed 12 weeks of treatment and reached the primary end-point of the study. |
|
|
| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To-Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on Patient Global Assessment were available only on: n=16 at week 4 and FU1, n=14 at week 6, week 12 and FU3, and n=12 at week 8 and week 10. Other data are missing. | Posted | Mean | Standard Deviation | units on a scale | 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. |
|
|
|
| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on Physician Global Assessment were available only on n=16 at week 4 and FU1, n=15 at FU3, n=14 at week 6 and week 12, n=12 at week 8 and week 10. Other data are missing. | Posted | Mean | Standard Deviation | units on a scale | 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. |
|
|
|
| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on N. joints with active arthritis were assessed only on: n=16 at week 4 and FU1, n=15 at FU3, n=14 at week 6 and week 12, n=12 at week 8 and week 10. Other data are missing. | Posted | Mean | Standard Deviation | units on a scale | 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. |
|
|
|
| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on N. joints with limitations were available only on: n=16 at week 4 and FU1, n=15 at FU3, n=14 at week 6 and week 12, n=12 at week 8 and week 10. Other data are missing. | Posted | Mean | Standard Deviation | units on a scale | 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. |
|
|
|
| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on CHAQ were available only on: n=16 at week 4 and FU1, n=14 at weeks 6, 12 and FU3, n=12 at weeks 8 and 10. Other data are missing. | Posted | Mean | Standard Deviation | units on a scale | 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. |
|
|
|
| Secondary | JIA Outcome Core Set Variables - ESR | Measurements of erythrocyte sedimentation rate (ESR) were performed at the local laboratory cooperating with each study site. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on ESR were available only on: n=16 at week 4 and FU1; n=13 at FU3, n=12 at week 8, n=10 at week 6 and n=8 at week 10. Other data are missing. | Posted | Mean | Standard Deviation | mm/hr | 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. |
|
|
|
| Secondary | Overall SFS Results - Sum of First Five Variables and Sum of Last Five Variables | Modified Systemic Feature Score (SFS) variables included:
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. | Per Protocol (PP) population: all pts who completed the study without any major protocol deviations Intent-To-Treat (ITT) population: all recruited pts who received medication for whom at least one safety or efficacy measurement is available. But, data on the sum of the first 5 variables were available on: n=16 at week 4; n=15 at FU1; n=14 at weeks 6, 12; n=12 at weeks 8, 10. Data on the sum of the last 5 variables were available on: n=14 at weeks 6, 12; n=12 at weeks 8, 10; n=16 at FU1. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Temperature | SFS variables included:
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). | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on T are available only on: n=16 at week 4; n=15 at FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Typical SOJIA Rash | SFS variables included:
Typical SOJIA is a salmon pink rash on the trunk during the febrile episodes. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Lymphadenopathy | SFS variables included:
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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Hepatomegaly and/or Splenomegaly | SFS variables included:
Hepatomegaly and/or splenomegaly was scored as present if confirmed by ultrasound evaluation and established after comparison to age standards for organ size. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Serositis | SFS variables included:
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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Erythrocyte Sedimentation Rate (ESR) | SFS variables included:
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%. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - C-reactive Protein (CRP) | SFS variables included:
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%. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
|
|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - White Blood Cell (WBC) | SFS variables included:
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%. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
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|
|
| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Haemoglobin (Hb) | SFS variables included:
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%. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
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| Secondary | Number of Patients With Presence or Absence of Each Item for Modified Systemic Feature Score (SFS) - Thrombocytes | SFS variables included:
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%. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. Nevertheless, data on this outcome are available only on: n=16 at week 4 and FU1; n=14 at week 12; n=12 at week 8. Other data are missing. | Posted | Number | participants | Pre-treatment, Weeks 4, 8, 12, and 1-month follow up |
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| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. | Posted | Number | participants | At weeks 2, 4, 6, 8, 10 and 12. |
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| Secondary | 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. | Per Protocol (PP) population: all patients who completed the study without any major deviations from the protocol procedures. Intent-To Treat (ITT) population: all recruited patients who received study medication and for whom at least one safety or efficacy measurement is available. | Posted | Number | participants | At week 4 |
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|
|
| 0 |
| 17 |
| 2 |
| 17 |
| 14 |
| 17 |
| Cellulitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA (11.1) | Systematic Assessment |
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| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (11.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (11.1) | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Enteritis | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Otitis media acute | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
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Not provided
Not provided
| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| FU1 |
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| FU3 |
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| Sum of first 5 (clinical) variables - Week 2 |
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| Sum of first 5 (clinical) variables - Week 4 |
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| Sum of first 5 (clinical) variables - Week 6 |
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| Sum of first 5 (clinical) variables - Week 8 |
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| Sum of first 5 (clinical) variables - Week 10 |
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| Sum of first 5 (clinical) variables - Week 12 |
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| Sum of first 5 (clinical) variables - FU1 |
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| Sum of last 5 (lab) variables - pretreatment |
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| Sum of last 5 (lab) variables - week 2 |
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| Sum of last 5 (lab) variables - week 4 |
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| Sum of last 5 (lab) variables - week 6 |
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| Sum of last 5 (lab) variables - week 8 |
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| Sum of last 5 (lab) variables - week 10 |
|
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| Sum of last 5 (lab) variables - week 12 |
|
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| Sum of last 5 (lab) variables - FU1 |
|
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| Temp - Pretreatment - presence |
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| Temp - Week 4 - absence |
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| Temp - Week 4 - presence |
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| Temp - Week 8 - absence |
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| Temp - Week 8 - presence |
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| Temp - Week 12 - absence |
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| Temp - Week 12 - presence |
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| Temp - FU1 - absence |
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| Temp - FU1 - presence |
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| Rash - Pretreatment - presence |
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| Rash - Week 4 - absence |
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| Rash - Week 4 - presence |
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| Rash - Week 8 - absence |
|
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| Rash - Week 8 - presence |
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| Rash - Week 12 - absence |
|
|
| Rash - Week 12 - presence |
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| Rash - FU1 - absence |
|
|
| Rash - FU1 - presence |
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| Lymphadenopathy - Pretreatment - presence |
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| Lymphadenopathy - Week 4 - absence |
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| Lymphadenopathy - Week 4 - presence |
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| Lymphadenopathy - Week 8 - absence |
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| Lymphadenopathy - Week 8 - presence |
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| Lymphadenopathy - Week 12 - absence |
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| Lymphadenopathy - Week 12 - presence |
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| Lymphadenopathy - FU1 - absence |
|
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| Lymphadenopathy - FU1 - presence |
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| Hepatomegaly - Pretreatment - presence |
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| Hepatomegaly - Week 4 - absence |
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| Hepatomegaly - Week 4 - presence |
|
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| Hepatomegaly - Week 8 - absence |
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| Hepatomegaly - Week 8 - presence |
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| Hepatomegaly - Week 12 - absence |
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| Hepatomegaly - Week 12 - presence |
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| Hepatomegaly - FU1 - absence |
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| Hepatomegaly - FU1 - presence |
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| Serositis - Pretreatment - presence |
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| Serositis - Week 4 - absence |
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| Serositis - Week 4 - presence |
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| Serositis - Week 8 - absence |
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| Serositis - Week 8 - presence |
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| Serositis - Week 12 - absence |
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| Serositis - Week 12 - presence |
|
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| Serositis - FU1 - absence |
|
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| Serositis - FU1 - presence |
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| ESR - Pretreatment - presence |
|
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| ESR - Week 4 - absence |
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| ESR - Week 4 - presence |
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| ESR - Week 8 - absence |
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| ESR - Week 8 - presence |
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| ESR - Week 12 - absence |
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| ESR - Week 12 - presence |
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| ESR - FU1 - absence |
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| ESR - FU1 - presence |
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| CRP - Pretreatment - presence |
|
|
| CRP - Week 4 - absence |
|
|
| CRP - Week 4 - presence |
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| CRP - Week 8 - absence |
|
|
| CRP - Week 8 - presence |
|
|
| CRP - Week 12 - absence |
|
|
| CRP - Week 12 - presence |
|
|
| CRP - FU1 - absence |
|
|
| CRP - FU1 - presence |
|
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| WBC - Pretreatment - presence |
|
|
| WBC - Week 4 - absence |
|
|
| WBC - Week 4 - presence |
|
|
| WBC - Week 8 - absence |
|
|
| WBC - Week 8 - presence |
|
|
| WBC - Week 12 - absence |
|
|
| WBC - Week 12 - presence |
|
|
| WBC - FU1 - absence |
|
|
| WBC - FU1 - presence |
|
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| Hb - Pretreatment - presence |
|
|
| Hb - Week 4 - absence |
|
|
| Hb - Week 4 - presence |
|
|
| Hb - Week 8 - absence |
|
|
| Hb - Week 8 - presence |
|
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| Hb - Week 12 - absence |
|
|
| WBC - Week 12 - presence |
|
|
| Hb - FU1 - absence |
|
|
| Hb - FU1 - presence |
|
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| Thrombocytes - Pretreatment - presence |
|
|
| Thrombocytes - Week 4 - absence |
|
|
| Thrombocytes - Week 4 - presence |
|
|
| Thrombocytes - Week 8 - absence |
|
|
| Thrombocytes - Week 8 - presence |
|
|
| Thrombocytes - Week 12 - absence |
|
|
| Thrombocytes - Week 12 - presence |
|
|
| Thrombocytes - FU1 - absence |
|
|
| Thrombocytes - FU1 - presence |
|
|
| JIA30 plus SFS - W4 - Clinical improvement |
|
| JIA30 plus SFS - W4 - Absence of clinical improvement |
|
| JIA30 plus SFS - W6 - Clinical improvement |
|
| JIA30 plus SFS - W6 - Absence of clinical improvement |
|
| JIA30 plus SFS - W8 - Clinical improvement |
|
| JIA30 plus SFS - W8 - Absence of clinical improvement |
|
| JIA30 plus SFS - W10 - Clinical improvement |
|
| JIA30 plus SFS - W10 - Absence of clinical improvement |
|
| JIA30 plus SFS - W12 - Clinical improvement |
|
| JIA30 plus SFS - W12 - Absence of clinical improvement |
|
| JIA50 plus SFS - W2 - Clinical improvement |
|
| JIA50 plus SFS - W2 - Absence of clinical improvement |
|
| JIA50 plus SFS - W4 - Clinical improvement |
|
| JIA50 plus SFS - W4 - Absence of clinical improvement |
|
| JIA50 plus SFS - W6 - Clinical improvement |
|
| JIA50 plus SFS - W6 - Absence of clinical improvement |
|
| JIA50 plus SFS - W8 - Clinical improvement |
|
| JIA50 plus SFS - W8 - Absence of clinical improvement |
|
| JIA50 plus SFS - W10 - Clinical improvement |
|
| JIA50 plus SFS - W10 - Absence of clinical improvement |
|
| JIA50 plus SFS - W12 - Clinical improvement |
|
| JIA50 plus SFS - W12 - Absence of clinical improvement |
|
| JIA70 plus SFS - W2 - Clinical improvement |
|
| JIA70 plus SFS - W2 - Absence of clinical improvement |
|
| JIA70 plus SFS - W4 - Clinical improvement |
|
| JIA70 plus SFS - W4 - Absence of clinical improvement |
|
| JIA70 plus SFS - W6 - Clinical improvement |
|
| JIA70 plus SFS - W6 - Absence of clinical improvement |
|
| JIA70 plus SFS - W8 - Clinical improvement |
|
| JIA70 plus SFS - W8 - Absence of clinical improvement |
|
| JIA70 plus SFS - W10 - Clinical improvement |
|
| JIA70 plus SFS - W10 - Absence of clinical improvement |
|
| JIA70 plus SFS - W12 - Clinical improvement |
|
| JIA70 plus SFS - W12 - Absence of clinical improvement |
|