Active Systemic Clinical Trial
— SOJIAOfficial title:
Phase II, Open Label, International, Multicentre Clinical Trial to Investigate Safety and Efficacy of Oral ITF2357 in Patients With Active Systemic Onset Juvenile Idiopathic Arthritis (SOJIA)
| Verified date | April 2021 |
| Source | Italfarmaco |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 17 |
| Est. completion date | June 10, 2013 |
| Est. primary completion date | August 25, 2008 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 25 Years |
| Eligibility | Inclusion Criteria: 1. Established diagnosis of Systemic SOJIA according to ILAR criteria for at least six months before the study entry, with inadequate response or intolerance to standard therapy with oral steroids and/or methotrexate, with or without previously used biologic agents. 2. Active disease for at least one month prior to enrolment as defined by the following criteria: - Presence of arthritis plus at least one of the following: - Fever, defined as a body temperature >= 37,5 C degree at least once a day during at least five consecutive days or presence of typical SOJIA intermittent temperature chart - Rash, defined by presence of typical SOJIA salmon pink rash on the trunk and elsewhere during the febrile episodes - Serositis (pericarditis, pleuritis, peritonitis) confirmed by ultrasound and/or X-ray exploration or by presence of typical ECG findings in the case of pericarditis - Lymphadenopathy, defined by lymph nodes enlargement to 1,5 cm or more localized anywhere within the body, and/or hepatomegaly and/or splenomegaly, confirmed by ultrasound evaluation and established after comparison to age standards for organ size - ESR >= 20 mm/h (first hour) and/or CRP >= 10 mg/L. in the absence of arthritis, two definite or one definite and one probable diagnostic criteria plus ESR >=20 mm/h (first hour) and/or CRP >=10 mg/L 3. Age at enrolment between 2 and 25 years 4. Age at first SOJIA diagnosis < 16 years 5. Previously introduced standard treatment of disease with steroids without satisfactory effect and concomitant treatment with oral steroids at a dose equivalent to >= 0,2 mg/kg/day of prednisolone, unmodified for at least four weeks before patient's enrolment 6. In case of concomitant methotrexate treatment, it has to be on stable dose >= 10mg/m2 weekly for al least 4 weeks before pt enrollment 7. Previous treatment with biologics, if any, during at least three months without satisfactory effect or with drug intolerability, discontinued for at least the period specified below before patient's enrolment: - Two months for etanercept - Six months for infliximab 8. Other disease-modifying anti-rheumatic drugs possibly previously introduced have to be discontinued for a period of at least five half lives 9. Concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at least four weeks before patient's enrolment 10. Female of childbearing potential, using safe contraceptive measures 11. Signed written informed consent before starting any study procedure Exclusion Criteria: 1. Ongoing clinical relevant viral infection (eg.: Herpes Zoster, Ebstein barr, CMV, Systemic fungal infections or history of recurrent serious bacterial infection) 2. History of macrophage activation syndrome 3. Clinically significant illness i.e. any condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study 4. Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements 5. Congenital heart and/or central nervous system disorders 6. Inherited metabolic diseases 7. Positive serological testing for anti HCV, anti HIV and HBsAg (to be performed at screening) 8. Pregnant or lactating women 9. Presence of malignancy 10. Any previous evidence, irrespective of its severity, of coronary disease, cardiac rhythm abnormalities or congestive heart failure 11. QTc interval > 450 msec at screening evaluation 12. Serum magnesium and potassium below the LLN at screening 13. Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes |
| Country | Name | City | State |
|---|---|---|---|
| Romania | Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni, | Bucharest | |
| Romania | Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district | Bucharest | |
| Serbia | Institute of Rheumatology Belgrade Resavska | Belgrade | |
| Serbia | Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica | Belgrade | Novi Belgrade |
| Serbia | University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica | Niš | Nis |
| Lead Sponsor | Collaborator |
|---|---|
| Italfarmaco |
Romania, Serbia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| 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. |
At week 12 | |
| 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. | 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. | 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. | 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. | 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. | 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. | 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: 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. |
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 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). |
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: 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. |
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: 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. |
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: 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. |
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: 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. |
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: 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%. |
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: 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%. |
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: 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%. |
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) - Haemoglobin (Hb) | SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit Hb was scored as present or not present according to the following criterion: Haemoglobin considered as lowered if below 11g/dL. At the subsequent visits Hb was scored 0 (Not present) if increased by 20% compared to pre-treatment value or normalized (> 11 g/dL); score 1 (Present) if decreased or increased less than 20%. |
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) - Thrombocytes | SFS variables included: temperature rash lymph nodes liver and spleen size clinical evidence of serositis (pericarditis, pleuritis or peritonitis) ESR CRP leukocyte count haemoglobin thrombocyte count At the pre-treatment visit thrombocyte count was scored as present or not present according to the following criterion: Thrombocyte count considered as increased if = 400x103/µL. At the subsequent visits thrombocyte count was scored 0 (Not present) if decreased by 20% compared to pretreatment value or normalized (< 400x103/µL); score 1 (Present) if increased or decreased less than 20%. |
Pre-treatment, Weeks 4, 8, 12, and 1-month follow up | |
| 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. |
At weeks 2, 4, 6, 8, 10 and 12. | |
| 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. | At week 4 |