SOJIA: Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients Completing Week 12 of Treatment [At week 12]
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 [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.]
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 [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.]
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 [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.]
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 [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.]
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 [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.]
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 [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.]
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 [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.]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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) [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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) [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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) [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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) [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [Pre-treatment, Weeks 4, 8, 12, and 1-month follow up]
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 [At weeks 2, 4, 6, 8, 10 and 12.]
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 [At week 4]
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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni, | Bucharest | Romania | 022328 | |
| 2 | Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district | Bucharest | Romania | 041451 | |
| 3 | University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica | Niš | Nis | Serbia | 18000 |
| 4 | Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica | Belgrade | Novi Belgrade | Serbia | 6-811070 |
| 5 | Institute of Rheumatology Belgrade Resavska | Belgrade | Serbia | 6911000 |
Sponsors and Collaborators
- Italfarmaco
Investigators
- Principal Investigator: Nemanja Damjanov, MD, PhD, Institute of Rheumatology Belgrade
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DSC/05/2357/19
Study Results
Participant Flow
| Recruitment Details | Seventeen patients were screened and enrolled in the study |
|---|---|
| Pre-assignment Detail | 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). |
| Arm/Group Title | ITF2357 |
|---|---|
| Arm/Group 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 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. |
| Period Title: Overall Study | |
| STARTED | 17 |
| COMPLETED | 10 |
| NOT COMPLETED | 7 |
Baseline Characteristics
| Arm/Group Title | ITF2357 |
|---|---|
| Arm/Group 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 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. |
| Overall Participants | 17 |
| Age (Count of Participants) | |
| <=18 years |
15
88.2%
|
| Between 18 and 65 years |
2
11.8%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
11.18
(5.39)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
6
35.3%
|
| Male |
11
64.7%
|
| Region of Enrollment (participants) [Number] | |
| Romania |
5
29.4%
|
| Serbia |
12
70.6%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Completers |
9
52.9%
|
10
NaN
|
| Non completers |
0
0%
|
7
NaN
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pre-treatment |
48.00
(22.50)
|
47.71
(21.45)
|
| Week 2 |
43.33
(21.15)
|
42.47
(21.30)
|
| Week 4 |
21.22
(14.00)
|
28.88
(22.48)
|
| Week 6 |
19.11
(15.00)
|
22.36
(18.33)
|
| Week 8 |
17.22
(14.59)
|
18.00
(13.99)
|
| Week 10 |
17.44
(13.28)
|
22.33
(19.58)
|
| Week 12 |
19.11
(14.57)
|
24.21
(20.89)
|
| FU1 |
18.11
(15.53)
|
26.56
(18.02)
|
| FU3 |
15.38
(15.32)
|
22.71
(17.85)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pretreatment |
48.00
(22.50)
|
47.71
(21.45)
|
| Week 2 |
43.33
(21.15)
|
42.47
(21.30)
|
| Week 4 |
21.22
(14.00)
|
28.88
(22.48)
|
| Week 6 |
19.11
(15.00)
|
22.36
(18.33)
|
| Week 8 |
17.22
(14.59)
|
18.00
(13.99)
|
| Week 10 |
17.44
(13.28)
|
22.33
(19.58)
|
| Week 12 |
19.11
(14.57)
|
24.21
(20.89)
|
| FU1 |
18.11
(15.53)
|
26.56
(18.02)
|
| FU3 |
15.38
(15.32)
|
22.71
(17.85)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pretreatment |
9.33
(8.70)
|
9.82
(9.11)
|
| Week 2 |
7.11
(8.62)
|
8.41
(9.49)
|
| Week 4 |
3.78
(5.47)
|
6.38
(9.26)
|
| Week 6 |
3.44
(5.29)
|
3.57
(4.33)
|
| Week 8 |
3.67
(4.85)
|
3.42
(4.29)
|
| Week 10 |
2.89
(4.54)
|
2.75
(4.03)
|
| Week 12 |
3.44
(4.59)
|
4.86
(4.74)
|
| FU1 |
3.00
(4.50)
|
3.88
(4.49)
|
| FU3 |
3.33
(4.58)
|
5.00
(6.05)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pretreatment |
10.00
(9.53)
|
11.59
(14.00)
|
| Week 2 |
8.56
(9.76)
|
10.41
(14.42)
|
| Week 4 |
6.44
(7.20)
|
7.44
(11.56)
|
| Week 6 |
5.78
(7.17)
|
7.86
(11.91)
|
| Week 8 |
5.78
(6.63)
|
4.67
(6.08)
|
| Week 10 |
5.22
(6.32)
|
4.42
(5.65)
|
| Week 12 |
4.78
(5.65)
|
8.79
(12.27)
|
| FU1 |
5.00
(5.92)
|
7.94
(12.22)
|
| FU3 |
5.22
(5.70)
|
7.20
(8.79)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pretreatment |
1.55
(0.54)
|
1.75
(0.74)
|
| Week 2 |
1.13
(0.57)
|
1.39
(0.87)
|
| Week 4 |
0.93
(0.55)
|
1.23
(0.88)
|
| Week 6 |
0.75
(0.56)
|
1.02
(0.82)
|
| Week 8 |
0.58
(0.50)
|
0.85
(0.82)
|
| Week 10 |
0.55
(0.50)
|
0.85
(0.87)
|
| Week 12 |
0.58
(0.41)
|
0.95
(0.82)
|
| FU1 |
0.56
(0.39)
|
1.02
(0.93)
|
| FU3 |
0.58
(0.51)
|
0.85
(0.78)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Pretreatment |
65.22
(23.05)
|
62.71
(31.76)
|
| Week 2 |
53.44
(26.54)
|
59.12
(30.90)
|
| Week 4 |
52.67
(22.66)
|
59.50
(34.71)
|
| Week 6 |
57.67
(20.66)
|
53.90
(22.35)
|
| Week 8 |
49.33
(33.78)
|
49.92
(31.20)
|
| Week 10 |
58.33
(23.40)
|
59.25
(23.35)
|
| Week 12 |
56.44
(40.76)
|
54.14
(37.07)
|
| FU1 |
39.89
(28.32)
|
46.31
(28.30)
|
| FU3 |
44.57
(25.00)
|
41.00
(25.02)
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Sum of first 5 (clinical) variables - pre-treatment |
1.33
(0.71)
|
0.94
(0.75)
|
| Sum of first 5 (clinical) variables - Week 2 |
0.44
(0.73)
|
0.35
(0.61)
|
| Sum of first 5 (clinical) variables - Week 4 |
0.11
(0.33)
|
0.31
(0.48)
|
| Sum of first 5 (clinical) variables - Week 6 |
0.11
(0.33)
|
0.14
(0.36)
|
| Sum of first 5 (clinical) variables - Week 8 |
0.11
(0.33)
|
0.17
(0.39)
|
| Sum of first 5 (clinical) variables - Week 10 |
0.11
(0.33)
|
0.33
(0.65)
|
| Sum of first 5 (clinical) variables - Week 12 |
0.22
(0.44)
|
0.29
(0.47)
|
| Sum of first 5 (clinical) variables - FU1 |
0.22
(0.44)
|
0.20
(0.41)
|
| Sum of last 5 (lab) variables - pretreatment |
4.33
(1.00)
|
4.24
(1.15)
|
| Sum of last 5 (lab) variables - week 2 |
2.44
(1.42)
|
2.65
(1.17)
|
| Sum of last 5 (lab) variables - week 4 |
2.11
(0.93)
|
2.25
(1.18)
|
| Sum of last 5 (lab) variables - week 6 |
1.56
(1.33)
|
1.93
(1.21)
|
| Sum of last 5 (lab) variables - week 8 |
2.00
(1.66)
|
1.92
(1.44)
|
| Sum of last 5 (lab) variables - week 10 |
2.00
(1.58)
|
2.08
(1.38)
|
| Sum of last 5 (lab) variables - week 12 |
1.89
(1.45)
|
2.07
(1.27)
|
| Sum of last 5 (lab) variables - FU1 |
2.22
(1.92)
|
2.56
(1.67)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Temp - Pretreatment - absence |
4
23.5%
|
10
NaN
|
| Temp - Pretreatment - presence |
5
29.4%
|
7
NaN
|
| Temp - Week 4 - absence |
8
47.1%
|
12
NaN
|
| Temp - Week 4 - presence |
1
5.9%
|
4
NaN
|
| Temp - Week 8 - absence |
8
47.1%
|
10
NaN
|
| Temp - Week 8 - presence |
1
5.9%
|
2
NaN
|
| Temp - Week 12 - absence |
7
41.2%
|
11
NaN
|
| Temp - Week 12 - presence |
2
11.8%
|
3
NaN
|
| Temp - FU1 - absence |
7
41.2%
|
12
NaN
|
| Temp - FU1 - presence |
2
11.8%
|
3
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Rash - Pretreatment - absence |
6
35.3%
|
14
NaN
|
| Rash - Pretreatment - presence |
3
17.6%
|
3
NaN
|
| Rash - Week 4 - absence |
9
52.9%
|
16
NaN
|
| Rash - Week 4 - presence |
0
0%
|
0
NaN
|
| Rash - Week 8 - absence |
9
52.9%
|
12
NaN
|
| Rash - Week 8 - presence |
0
0%
|
0
NaN
|
| Rash - Week 12 - absence |
9
52.9%
|
14
NaN
|
| Rash - Week 12 - presence |
0
0%
|
0
NaN
|
| Rash - FU1 - absence |
9
52.9%
|
16
NaN
|
| Rash - FU1 - presence |
0
0%
|
0
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Lymphadenopathy - Pretreatment - absence |
6
35.3%
|
13
NaN
|
| Lymphadenopathy - Pretreatment - presence |
3
17.6%
|
4
NaN
|
| Lymphadenopathy - Week 4 - absence |
9
52.9%
|
16
NaN
|
| Lymphadenopathy - Week 4 - presence |
0
0%
|
0
NaN
|
| Lymphadenopathy - Week 8 - absence |
9
52.9%
|
12
NaN
|
| Lymphadenopathy - Week 8 - presence |
0
0%
|
0
NaN
|
| Lymphadenopathy - Week 12 - absence |
9
52.9%
|
14
NaN
|
| Lymphadenopathy - Week 12 - presence |
0
0%
|
0
NaN
|
| Lymphadenopathy - FU1 - absence |
9
52.9%
|
16
NaN
|
| Lymphadenopathy - FU1 - presence |
0
0%
|
0
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Hepatomegaly - Pretreatment - absence |
8
47.1%
|
16
NaN
|
| Hepatomegaly - Pretreatment - presence |
1
5.9%
|
1
NaN
|
| Hepatomegaly - Week 4 - absence |
9
52.9%
|
16
NaN
|
| Hepatomegaly - Week 4 - presence |
0
0%
|
0
NaN
|
| Hepatomegaly - Week 8 - absence |
9
52.9%
|
12
NaN
|
| Hepatomegaly - Week 8 - presence |
0
0%
|
0
NaN
|
| Hepatomegaly - Week 12 - absence |
9
52.9%
|
14
NaN
|
| Hepatomegaly - Week 12 - presence |
0
0%
|
0
NaN
|
| Hepatomegaly - FU1 - absence |
9
52.9%
|
16
NaN
|
| Hepatomegaly - FU1 - presence |
0
0%
|
0
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Serositis - Pretreatment - absence |
9
52.9%
|
16
NaN
|
| Serositis - Pretreatment - presence |
0
0%
|
1
NaN
|
| Serositis - Week 4 - absence |
9
52.9%
|
15
NaN
|
| Serositis - Week 4 - presence |
0
0%
|
1
NaN
|
| Serositis - Week 8 - absence |
9
52.9%
|
12
NaN
|
| Serositis - Week 8 - presence |
0
0%
|
0
NaN
|
| Serositis - Week 12 - absence |
9
52.9%
|
13
NaN
|
| Serositis - Week 12 - presence |
0
0%
|
1
NaN
|
| Serositis - FU1 - absence |
9
52.9%
|
16
NaN
|
| Serositis - FU1 - presence |
0
0%
|
0
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| ESR - Pretreatment - absence |
0
0%
|
1
NaN
|
| ESR - Pretreatment - presence |
9
52.9%
|
16
NaN
|
| ESR - Week 4 - absence |
2
11.8%
|
5
NaN
|
| ESR - Week 4 - presence |
7
41.2%
|
11
NaN
|
| ESR - Week 8 - absence |
4
23.5%
|
4
NaN
|
| ESR - Week 8 - presence |
5
29.4%
|
8
NaN
|
| ESR - Week 12 - absence |
3
17.6%
|
5
NaN
|
| ESR - Week 12 - presence |
6
35.3%
|
9
NaN
|
| ESR - FU1 - absence |
4
23.5%
|
6
NaN
|
| ESR - FU1 - presence |
5
29.4%
|
10
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| CRP - Pretreatment - absence |
0
0%
|
0
NaN
|
| CRP - Pretreatment - presence |
9
52.9%
|
17
NaN
|
| CRP - Week 4 - absence |
5
29.4%
|
8
NaN
|
| CRP - Week 4 - presence |
4
23.5%
|
8
NaN
|
| CRP - Week 8 - absence |
4
23.5%
|
6
NaN
|
| CRP - Week 8 - presence |
5
29.4%
|
6
NaN
|
| CRP - Week 12 - absence |
5
29.4%
|
6
NaN
|
| CRP - Week 12 - presence |
4
23.5%
|
8
NaN
|
| CRP - FU1 - absence |
6
35.3%
|
10
NaN
|
| CRP - FU1 - presence |
3
17.6%
|
6
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| WBC - Pretreatment - absence |
2
11.8%
|
4
NaN
|
| WBC - Pretreatment - presence |
7
41.2%
|
13
NaN
|
| WBC - Week 4 - absence |
6
35.3%
|
10
NaN
|
| WBC - Week 4 - presence |
3
17.6%
|
6
NaN
|
| WBC - Week 8 - absence |
7
41.2%
|
10
NaN
|
| WBC - Week 8 - presence |
2
11.8%
|
2
NaN
|
| WBC - Week 12 - absence |
7
41.2%
|
10
NaN
|
| WBC - Week 12 - presence |
2
11.8%
|
4
NaN
|
| WBC - FU1 - absence |
5
29.4%
|
6
NaN
|
| WBC - FU1 - presence |
4
23.5%
|
10
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Hb - Pretreatment - absence |
3
17.6%
|
6
NaN
|
| Hb - Pretreatment - presence |
6
35.3%
|
11
NaN
|
| Hb - Week 4 - absence |
4
23.5%
|
6
NaN
|
| Hb - Week 4 - presence |
5
29.4%
|
10
NaN
|
| Hb - Week 8 - absence |
4
23.5%
|
6
NaN
|
| Hb - Week 8 - presence |
5
29.4%
|
6
NaN
|
| Hb - Week 12 - absence |
4
23.5%
|
6
NaN
|
| WBC - Week 12 - presence |
5
29.4%
|
8
NaN
|
| Hb - FU1 - absence |
4
23.5%
|
8
NaN
|
| Hb - FU1 - presence |
5
29.4%
|
8
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Thrombocytes - Pretreatment - absence |
1
5.9%
|
2
NaN
|
| Thrombocytes - Pretreatment - presence |
8
47.1%
|
15
NaN
|
| Thrombocytes - Week 4 - absence |
9
52.9%
|
15
NaN
|
| Thrombocytes - Week 4 - presence |
0
0%
|
1
NaN
|
| Thrombocytes - Week 8 - absence |
8
47.1%
|
11
NaN
|
| Thrombocytes - Week 8 - presence |
1
5.9%
|
1
NaN
|
| Thrombocytes - Week 12 - absence |
9
52.9%
|
14
NaN
|
| Thrombocytes - Week 12 - presence |
0
0%
|
0
NaN
|
| Thrombocytes - FU1 - absence |
6
35.3%
|
9
NaN
|
| Thrombocytes - FU1 - presence |
3
17.6%
|
7
NaN
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| JIA30 plus SFS - W2 - Clinical improvement |
7
41.2%
|
11
NaN
|
| JIA30 plus SFS - W2 - Absence of clinical improvement |
2
11.8%
|
6
NaN
|
| JIA30 plus SFS - W4 - Clinical improvement |
8
47.1%
|
12
NaN
|
| JIA30 plus SFS - W4 - Absence of clinical improvement |
1
5.9%
|
5
NaN
|
| JIA30 plus SFS - W6 - Clinical improvement |
8
47.1%
|
12
NaN
|
| JIA30 plus SFS - W6 - Absence of clinical improvement |
1
5.9%
|
5
NaN
|
| JIA30 plus SFS - W8 - Clinical improvement |
8
47.1%
|
11
NaN
|
| JIA30 plus SFS - W8 - Absence of clinical improvement |
1
5.9%
|
6
NaN
|
| JIA30 plus SFS - W10 - Clinical improvement |
8
47.1%
|
11
NaN
|
| JIA30 plus SFS - W10 - Absence of clinical improvement |
1
5.9%
|
6
NaN
|
| JIA30 plus SFS - W12 - Clinical improvement |
8
47.1%
|
10
NaN
|
| JIA30 plus SFS - W12 - Absence of clinical improvement |
1
5.9%
|
7
NaN
|
| JIA50 plus SFS - W2 - Clinical improvement |
7
41.2%
|
11
NaN
|
| JIA50 plus SFS - W2 - Absence of clinical improvement |
2
11.8%
|
6
NaN
|
| JIA50 plus SFS - W4 - Clinical improvement |
8
47.1%
|
10
NaN
|
| JIA50 plus SFS - W4 - Absence of clinical improvement |
1
5.9%
|
7
NaN
|
| JIA50 plus SFS - W6 - Clinical improvement |
8
47.1%
|
11
NaN
|
| JIA50 plus SFS - W6 - Absence of clinical improvement |
1
5.9%
|
6
NaN
|
| JIA50 plus SFS - W8 - Clinical improvement |
8
47.1%
|
10
NaN
|
| JIA50 plus SFS - W8 - Absence of clinical improvement |
1
5.9%
|
7
NaN
|
| JIA50 plus SFS - W10 - Clinical improvement |
8
47.1%
|
9
NaN
|
| JIA50 plus SFS - W10 - Absence of clinical improvement |
1
5.9%
|
8
NaN
|
| JIA50 plus SFS - W12 - Clinical improvement |
8
47.1%
|
9
NaN
|
| JIA50 plus SFS - W12 - Absence of clinical improvement |
1
5.9%
|
8
NaN
|
| JIA70 plus SFS - W2 - Clinical improvement |
6
35.3%
|
10
NaN
|
| JIA70 plus SFS - W2 - Absence of clinical improvement |
3
17.6%
|
7
NaN
|
| JIA70 plus SFS - W4 - Clinical improvement |
8
47.1%
|
10
NaN
|
| JIA70 plus SFS - W4 - Absence of clinical improvement |
1
5.9%
|
7
NaN
|
| JIA70 plus SFS - W6 - Clinical improvement |
8
47.1%
|
10
NaN
|
| JIA70 plus SFS - W6 - Absence of clinical improvement |
1
5.9%
|
7
NaN
|
| JIA70 plus SFS - W8 - Clinical improvement |
8
47.1%
|
9
NaN
|
| JIA70 plus SFS - W8 - Absence of clinical improvement |
1
5.9%
|
8
NaN
|
| JIA70 plus SFS - W10 - Clinical improvement |
8
47.1%
|
9
NaN
|
| JIA70 plus SFS - W10 - Absence of clinical improvement |
1
5.9%
|
8
NaN
|
| JIA70 plus SFS - W12 - Clinical improvement |
8
47.1%
|
9
NaN
|
| JIA70 plus SFS - W12 - Absence of clinical improvement |
1
5.9%
|
8
NaN
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ITF2357 - PP Population | ITF2357 - ITT Population |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 17 |
| Therapeutic response |
8
47.1%
|
11
NaN
|
| Absence of therapeutic response |
1
5.9%
|
6
NaN
|
Adverse Events
| Time Frame | At weeks 1, 2, 4, 6, 8, 10, 12 (end of treatment) and FU1 and FU3 | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | IT2357 - Safety Population | |
| Arm/Group Description | Safety population: all recruited patients who received at least one dose of the study medication. | |
All Cause Mortality |
||
| IT2357 - Safety Population | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | |
Serious Adverse Events |
||
| IT2357 - Safety Population | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/17 (11.8%) | |
| Infections and infestations | ||
| Varicella | 1/17 (5.9%) | 1 |
| Cellulitis | 1/17 (5.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| IT2357 - Safety Population | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/17 (82.4%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 1/17 (5.9%) | 1 |
| Enteritis | 1/17 (5.9%) | 1 |
| Nausea | 1/17 (5.9%) | 6 |
| Vomiting | 1/17 (5.9%) | 3 |
| General disorders | ||
| Fatigue | 1/17 (5.9%) | 1 |
| Pyrexia | 1/17 (5.9%) | 1 |
| Infections and infestations | ||
| Influenza | 2/17 (11.8%) | 2 |
| Nasopharyngitis | 1/17 (5.9%) | 1 |
| Otitis media | 1/17 (5.9%) | 1 |
| Otitis media acute | 1/17 (5.9%) | 1 |
| Pharyngitis | 1/17 (5.9%) | 1 |
| Tonsillitis | 1/17 (5.9%) | 2 |
| Injury, poisoning and procedural complications | ||
| Injury | 1/17 (5.9%) | 1 |
| Investigations | ||
| Electrocardiogram QT prolonged | 1/17 (5.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/17 (5.9%) | 1 |
| Arthritis | 3/17 (17.6%) | 3 |
| Joint swelling | 1/17 (5.9%) | 3 |
| Psychiatric disorders | ||
| Depression | 1/17 (5.9%) | 1 |
| Renal and urinary disorders | ||
| Haematuria | 1/17 (5.9%) | 1 |
| Nephrolithiasis | 1/17 (5.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Atelectasis | 1/17 (5.9%) | 1 |
| Oropharyngeal pain | 3/17 (17.6%) | 3 |
| Skin and subcutaneous tissue disorders | ||
| Dermatitis contact | 1/17 (5.9%) | 1 |
| Rash | 2/17 (11.8%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Maurizio Caserini, MD |
|---|---|
| Organization | Italfarmaco SpA |
| Phone | +39 0264431 |
| m.caserini@italfarmaco.com |
- DSC/05/2357/19