MedPath

A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Phase 3
Completed
Conditions
Juvenile Idiopathic Arthritis
Interventions
Drug: Tocilizumab
Drug: Placebo
Registration Number
NCT00988221
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients \< 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
188
Inclusion Criteria
  • Children/juveniles, 2-17 years of age.
  • Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
  • Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
  • Inadequate response to or inability to tolerate methotrexate.
  • Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
  • Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.
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Exclusion Criteria
  • Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
  • Wheelchair bound or bedridden.
  • Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
  • Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
  • Previous treatment with tocilizumab.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tocilizumab 10 mg/kg in patients weighing < 30 kgTocilizumabPatients received tocilizumab 10 mg/kg intravenously every 4 weeks.
Tocilizumab 8 mg/kg in patients weighing < 30 kgTocilizumabPatients received tocilizumab 8 mg/kg intravenously every 4 weeks.
PlaceboPlaceboPatients received placebo to tocilizumab intravenously every 4 weeks.
Tocilizumab 8 mg/kg in patients weighing ≥ 30 kgTocilizumabPatients received tocilizumab 8 mg/kg intravenously every 4 weeks.
Primary Outcome Measures
NameTimeMethod
Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)Week 16 through Week 40

JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving \> 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.

Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16)Baseline to Week 16

Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16)Week 16

A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (\< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16)Baseline to Week 16

Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16)Baseline to Week 16

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16)Baseline to Week 16

Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.

Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16)Week 16

The JADAS-27 is derived from the following components: Physician's global assessment of disease activity on a 0-100 mm visual analog scale (VAS)/10, patient/parent's global assessment of overall well-being on a 0-100 mm VAS/10, normalized erythrocyte sedimentation rate (ESR) (if ESR is ≤ 20 then set to 0, if ≥ 120 then set to 10, and if \> 20 and \< 120 then apply formula \[ESR-20\]/10), and number of joints (maximum of 27) with active arthritis (cervical spine, left/right elbow, left/right wrist, left/right MCP1-3, left/right PIP1-5, left/right hips, left/right knee and left/right ankle). The scores for the first 3 components range from 0-10; the score for the final component ranges from 0-27. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16)Week 16

The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain.

Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16)Baseline to Week 16

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)Baseline to Week 16

Platelets were measured in blood samples taken from the patients.

Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)Baseline to Week 16

White blood cells were measured in blood samples taken from the patients.

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)Baseline to Week 16

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]).

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16)Baseline to Week 16

The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16)Baseline to Week 16

The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement.

Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16)Baseline to Week 16

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.

Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40)Week 40

A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (\< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.

The statistical test is not significant due to a break in the hierarchical chain of significance testing.

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104Week 2 to Week 104

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]).

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40)Week 40

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40)Baseline to Week 40

The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40)Baseline to Week 40

The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40)Baseline to Week 40

Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40)Baseline to Week 40

Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40)Baseline to Week 40

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40)Baseline to Week 40

The Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40)Baseline to Week 40

The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward (LOCF) imputation for missing values. The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids, and the pain visual analog scale score at Baseline. The adjusted means from the fitted model are presented.

Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104Week 104

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). Results are reported for the subgroups: Previous biologic treatment (yes/no), concomitant methotrexate use (yes/no), rheumatoid factor (positive/negative), concomitant oral corticosteroid use (yes/no). Last observation carried forward was applied to missing components at visits.

Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104Baseline to Week 104

The JADAS-71 is composed of 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range = 0-10, left end of the line = arthritis inactive, ie, symptom-free and no arthritis symptoms; right end = arthritis very active), patient/parent global assessment of overall well-being on a VAS (range = 0-10, left end of the line = very well, ie, symptom-free and no arthritis disease activity; right end = very poor, ie, maximum arthritis disease activity), normalized erythrocyte sedimentation rate (ESR) (range = 0-10, If ESR is ≤ 20 mm/h, set to 0. If ≥ 120 mm/h, set to 10 mm/h. If \> 20 mm/h and \< 120 mm/h, apply formula: \[ESR - 20 mm/h\]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). The JADAS-71 is the sum of the 4 component scores and ranges from 0-101. A higher score indicates more arthritis disease activity. A positive change score indicates improvement.

Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104Baseline to Week 104

The CHAQ-DI consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A minimally important improvement is an improvement ≥ 0.13 over Baseline. Patients who withdrew due to non-safety reasons are classified as non-responders.

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104Baseline to Week 104

The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104Baseline to Week 104

The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104Baseline to Week 104

Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104Baseline to Week 104

Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104Baseline to Week 104

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104Baseline to Week 104

The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104Baseline to Week 104

Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

C-reactive Protein Levels From Baseline to Week 104Baseline to Week 104

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Percent of Patients With Inactive Disease From Week 16 to Week 104Week 16 to Week 104

A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (\< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.

Percent of Patients in Clinical Remission From Week 40 to 104Week 40 to Week 104

A patient was in clinical remission if they had inactive disease at all visits in the 6 months prior to and including the visit assessment day. A patient was judged to have inactive disease if all of the following criteria were met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (\< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years)Baseline to Week 104

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). Patients who withdrew due to non-safety reasons are classified as non-responders.

Methotrexate Dose at Baseline, Week 52, and Week 104Baseline to Week 104

Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.

Oral Corticosteroid Dose at Baseline, Week 52, and Week 104Baseline to Week 104

Due to the different types of corticosteroid medications available, the prednisone equivalent was used in the calculation of the oral corticosteroid dose. Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.

Height Standard Deviation Score at Baseline, Week 52, and Week 104Baseline to Week 104

The height Standard Deviation Score was calculated using the following formula: (Observed height - median of the reference population)/standard deviation of the reference population. The reference population was defined as that of the same sex and age to the nearest completed year and month using the World Health Organization norms. A negative score indicates less height than the reference population.

Trial Locations

Locations (69)

Princess Margaret Children'S Hospital; Department of Immunology

🇦🇺

Subiaco, Western Australia, Australia

Alberta Children'S Hospital

🇨🇦

Calgary, Alberta, Canada

Children'S Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

Hospital For Sick Children

🇨🇦

Toronto, Ontario, Canada

Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny

🇵🇱

Sosnowiec, Poland

Delray Research Associates

🇺🇸

Delray Beach, Florida, United States

Instituto Nacional De Salud Del Niño

🇵🇪

Lima, Peru

Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci

🇵🇱

Lodz, Poland

Southern District Medical Center of Roszdrav

🇷🇺

Rostov-Na-Donu, Russian Federation

Saint-Petersburg State; Pediatrics Medical Academy

🇷🇺

Saint-Petersburg, Russian Federation

University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit

🇺🇸

Louisville, Kentucky, United States

Clinica San Borja; Servicio De Reumatologia

🇵🇪

Lima, Peru

Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych

🇵🇱

Kraków, Poland

Dzieciecy Szpital Kliniczny IM. Prof. A. Gebali; Oddzial Pediatrii Chorob Pluc I Reumatologii

🇵🇱

Lublin, Poland

Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher

🇵🇱

Warszawa, Poland

FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences

🇷🇺

Moscow, Russian Federation

Bristol Royal Hospital For Children

🇬🇧

Bristol, United Kingdom

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

🇪🇸

Valencia, Spain

Cliditer SA de CV

🇲🇽

Miexico City, Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

🇲🇽

Monterrey, Mexico

Clinica San Felipe; Consultorio de Reumatología

🇵🇪

Lima, Peru

Hospital Universitario Reina Sofia; Servicio de Reumatologia

🇪🇸

Cordoba, Spain

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

🇪🇸

Madrid, Spain

Cif Biotec Medica Sur

🇲🇽

Mexico City, Distrito Federal, Mexico

Inst. Mexicano de Investigacion Clinica

🇲🇽

Mexico City, Mexico

Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego

🇵🇱

Bydgoszcz, Poland

I. M. Sechenov Moscow State Medical University; The Ministry of Health and Social Development of RF

🇷🇺

Moscow, Russian Federation

Samara Regional Clinical Cardiology Dispensary

🇷🇺

Samara, Russian Federation

Hospital Universitario Virgen Macarena; Servicio de Reumatologia

🇪🇸

Sevilla, Spain

UZ Gent

🇧🇪

Gent, Belgium

Hospital Ramon y Cajal ; Servicio de Reumatologia

🇪🇸

Madrid, Spain

Great Ormond Street Hospital for Sick Children; Institute of Child Health

🇬🇧

London, United Kingdom

Royal Liverpool Childrens Hospital; Rheumatology

🇬🇧

Liverpool, United Kingdom

Children's National Medical Center; Pediatric Rheumatology

🇺🇸

Washington, D.C., District of Columbia, United States

Connecticut Children's Medical Center; 5E Clinical Trials Unit

🇺🇸

Hartford, Connecticut, United States

The University of Chicago;Department of Pediatrics

🇺🇸

Chicago, Illinois, United States

Hackensack University Medical Center; Pediatric Rheumatology

🇺🇸

Hackensack, New Jersey, United States

Children's Hospital

🇺🇸

New Orleans, Louisiana, United States

Healthcare Research Consultants

🇺🇸

Tulsa, Oklahoma, United States

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

🇺🇸

Cincinnati, Ohio, United States

Hospital Gral de Niños Pedro Elizalde

🇦🇷

Buenos Aires, Argentina

Hospital de Niños; Reumatologia

🇦🇷

Buenos Aires, Argentina

Centro Medico Privado de Reumatologia; Reumathology

🇦🇷

San Miguel, Argentina

Caici; Rheumatology

🇦🇷

Rosario, Argentina

Westmead Hospital; Paediatric Rheumatology

🇦🇺

Westmead, New South Wales, Australia

Royal Children'S Hospital; Paediatric Rheumatology

🇦🇺

Parkville, Victoria, Australia

UZ Leuven Gasthuisberg

🇧🇪

Leuven, Belgium

Hospital das Clinicas - UFRGS

🇧🇷

Porto Alegre, RS, Brazil

Hospital Universitario Pedro Ernesto; Nucleo de Estudos da Saude do Adolescente

🇧🇷

Rio de janeiro, RJ, Brazil

Instituto de Puericultura E Pediatria Martagão Gesteira

🇧🇷

Rio de Janeiro, RJ, Brazil

Hôpital Pellegrin; Urgences Pédiatriques

🇫🇷

Bordeaux, France

British Columbia Children's Hospital; Rheumatology

🇨🇦

Vancouver, British Columbia, Canada

Hopital Cochin; Rhumatologie A

🇫🇷

Paris, France

CH de Bicêtre; Pediatrie Generale

🇫🇷

Le Kremlin Bicêtre, France

Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen

🇫🇷

Montpellier, France

Hop Necker Enfants Malades;UIH

🇫🇷

Paris, France

Charité Campus; Virchow Klinikum Berlin

🇩🇪

Berlin, Germany

Hopitaux De Brabois; Medecine Infantile II

🇫🇷

Vandoeuvre Les Nancy, France

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

🇩🇪

Bremen, Germany

Clementine Hospital; Kinder- und Jugendrheumatologie

🇩🇪

Frankfurt/Main, Germany

Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie

🇩🇪

Sankt Augustin, Germany

ASST CENTRO SPECIALISTICO ORTOPEDICO TRAUMATO-LOGICO GAETANO PINI/CTO; Reumatol. Pediatrica

🇮🇹

Milano, Lombardia, Italy

IRCCS G. Gaslini; Pediatria II

🇮🇹

Genova, Liguria, Italy

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

🇮🇹

Roma, Lazio, Italy

Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

🇮🇹

Padova, Veneto, Italy

Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°

🇮🇹

Firenze, Toscana, Italy

SI Sceintific children health center RAMS

🇷🇺

Moscow, Russian Federation

Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia

🇧🇷

Sao Paulo, SP, Brazil

Miami Children's Hospital

🇺🇸

Miami, Florida, United States

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