Please note that the ANZCTR website will be unavailable from 9am until 9.30am (AEST) on Monday 22nd July for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00988221




Registration number
NCT00988221
Ethics application status
Date submitted
1/10/2009
Date registered
2/10/2009
Date last updated
26/07/2017

Titles & IDs
Public title
A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis
Scientific title
A 24 Week Randomized, Double-blind, Placebo-controlled Withdrawal Trial With a 16 Week Open-label lead-in Phase, and 64 Week Open-label Follow-up, to Evaluate the Effect on Clinical Response and the Safety of Tocilizumab in Patients With Active Polyarticular-course Juvenile Idiopathic Arthritis
Secondary ID [1] 0 0
2009-011593-15
Secondary ID [2] 0 0
WA19977
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Juvenile Idiopathic Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Placebo

Experimental: Tocilizumab 10 mg/kg in patients weighing < 30 kg - Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.

Experimental: Tocilizumab 8 mg/kg in patients weighing < 30 kg - Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Experimental: Tocilizumab 8 mg/kg in patients weighing = 30 kg - Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Placebo Comparator: Placebo - Patients received placebo to tocilizumab intravenously every 4 weeks.


Treatment: Drugs: Tocilizumab
Tocilizumab was supplied as a sterile solution in vials.

Treatment: Drugs: Placebo
Placebo to tocilizumab was supplied as a sterile solution in vials.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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) - 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.
Timepoint [1] 0 0
Week 16 through Week 40
Secondary outcome [1] 0 0
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) - 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]).
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [2] 0 0
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) - 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.
Timepoint [2] 0 0
Baseline to Week 16
Secondary outcome [3] 0 0
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) - 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.
Timepoint [3] 0 0
Baseline to Week 16
Secondary outcome [4] 0 0
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) - 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.
Timepoint [4] 0 0
Baseline to Week 16
Secondary outcome [5] 0 0
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) - 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.
Timepoint [5] 0 0
Baseline to Week 16
Secondary outcome [6] 0 0
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) - Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
Timepoint [6] 0 0
Baseline to Week 16
Secondary outcome [7] 0 0
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) - 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.
Timepoint [7] 0 0
Baseline to Week 16
Secondary outcome [8] 0 0
Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (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.
Timepoint [8] 0 0
Week 16
Secondary outcome [9] 0 0
Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (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.
Timepoint [9] 0 0
Week 16
Secondary outcome [10] 0 0
Percent of Patients With Inactive Disease at the End of Part I of the Study (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.
Timepoint [10] 0 0
Week 16
Secondary outcome [11] 0 0
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) - C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
Timepoint [11] 0 0
Baseline to Week 16
Secondary outcome [12] 0 0
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) - Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.
Timepoint [12] 0 0
Baseline to Week 16
Secondary outcome [13] 0 0
Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16) - Platelets were measured in blood samples taken from the patients.
Timepoint [13] 0 0
Baseline to Week 16
Secondary outcome [14] 0 0
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) - White blood cells were measured in blood samples taken from the patients.
Timepoint [14] 0 0
Baseline to Week 16
Secondary outcome [15] 0 0
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) - 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.
Timepoint [15] 0 0
Week 40
Secondary outcome [16] 0 0
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) - 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.
Timepoint [16] 0 0
Baseline to Week 40
Secondary outcome [17] 0 0
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) - 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.
Timepoint [17] 0 0
Baseline to Week 40
Secondary outcome [18] 0 0
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) - 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.
Timepoint [18] 0 0
Baseline to Week 40
Secondary outcome [19] 0 0
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) - 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.
Timepoint [19] 0 0
Baseline to Week 40
Secondary outcome [20] 0 0
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) - 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.
Timepoint [20] 0 0
Baseline to Week 40
Secondary outcome [21] 0 0
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) - 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.
Timepoint [21] 0 0
Baseline to Week 40
Secondary outcome [22] 0 0
Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (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.
Timepoint [22] 0 0
Baseline to Week 40
Secondary outcome [23] 0 0
Percent of Patients With Inactive Disease at the End of Part II of the Study (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.
Timepoint [23] 0 0
Week 40
Secondary outcome [24] 0 0
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 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]).
Timepoint [24] 0 0
Week 2 to Week 104
Secondary outcome [25] 0 0
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 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.
Timepoint [25] 0 0
Week 104
Secondary outcome [26] 0 0
Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at 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.
Timepoint [26] 0 0
Baseline to Week 104
Secondary outcome [27] 0 0
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 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.
Timepoint [27] 0 0
Baseline to Week 104
Secondary outcome [28] 0 0
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 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.
Timepoint [28] 0 0
Baseline to Week 104
Secondary outcome [29] 0 0
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 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.
Timepoint [29] 0 0
Baseline to Week 104
Secondary outcome [30] 0 0
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 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.
Timepoint [30] 0 0
Baseline to Week 104
Secondary outcome [31] 0 0
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at 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.
Timepoint [31] 0 0
Baseline to Week 104
Secondary outcome [32] 0 0
Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at 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.
Timepoint [32] 0 0
Baseline to Week 104
Secondary outcome [33] 0 0
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 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.
Timepoint [33] 0 0
Baseline to Week 104
Secondary outcome [34] 0 0
C-reactive Protein Levels From Baseline 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.
Timepoint [34] 0 0
Baseline to Week 104
Secondary outcome [35] 0 0
Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 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.
Timepoint [35] 0 0
Baseline to Week 104
Secondary outcome [36] 0 0
Percent of Patients With Inactive Disease From Week 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.
Timepoint [36] 0 0
Week 16 to Week 104
Secondary outcome [37] 0 0
Percent of Patients in Clinical Remission From Week 40 to 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.
Timepoint [37] 0 0
Week 40 to Week 104
Secondary outcome [38] 0 0
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) - 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.
Timepoint [38] 0 0
Baseline to Week 104
Secondary outcome [39] 0 0
Oral Corticosteroid Dose at Baseline, Week 52, and 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.
Timepoint [39] 0 0
Baseline to Week 104
Secondary outcome [40] 0 0
Methotrexate Dose at Baseline, Week 52, and 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.
Timepoint [40] 0 0
Baseline to Week 104
Secondary outcome [41] 0 0
Height Standard Deviation Score at Baseline, Week 52, and 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.
Timepoint [41] 0 0
Baseline to Week 104

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital; Paediatric Rheumatology - Westmead
Recruitment hospital [2] 0 0
Royal Children'S Hospital; Paediatric Rheumatology - Parkville
Recruitment hospital [3] 0 0
Princess Margaret Children'S Hospital; Department of Immunology - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Rosario
Country [12] 0 0
Argentina
State/province [12] 0 0
San Miguel
Country [13] 0 0
Belgium
State/province [13] 0 0
Gent
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Brazil
State/province [15] 0 0
RJ
Country [16] 0 0
Brazil
State/province [16] 0 0
RS
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
France
State/province [21] 0 0
Bordeaux
Country [22] 0 0
France
State/province [22] 0 0
Le Kremlin Bicêtre
Country [23] 0 0
France
State/province [23] 0 0
Montpellier
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
Vandoeuvre Les Nancy
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Bremen
Country [28] 0 0
Germany
State/province [28] 0 0
Frankfurt/Main
Country [29] 0 0
Germany
State/province [29] 0 0
Sankt Augustin
Country [30] 0 0
Italy
State/province [30] 0 0
Lazio
Country [31] 0 0
Italy
State/province [31] 0 0
Liguria
Country [32] 0 0
Italy
State/province [32] 0 0
Lombardia
Country [33] 0 0
Italy
State/province [33] 0 0
Toscana
Country [34] 0 0
Italy
State/province [34] 0 0
Veneto
Country [35] 0 0
Mexico
State/province [35] 0 0
Mexico City, Distrito Federal
Country [36] 0 0
Mexico
State/province [36] 0 0
Mexico City
Country [37] 0 0
Mexico
State/province [37] 0 0
Miexico City
Country [38] 0 0
Mexico
State/province [38] 0 0
Monterrey
Country [39] 0 0
Peru
State/province [39] 0 0
Lima
Country [40] 0 0
Poland
State/province [40] 0 0
Bydgoszcz
Country [41] 0 0
Poland
State/province [41] 0 0
Kraków
Country [42] 0 0
Poland
State/province [42] 0 0
Lodz
Country [43] 0 0
Poland
State/province [43] 0 0
Lublin
Country [44] 0 0
Poland
State/province [44] 0 0
Sosnowiec
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Moscow
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Rostov-Na-Donu
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Saint-Petersburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Samara
Country [50] 0 0
Spain
State/province [50] 0 0
Cordoba
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Sevilla
Country [53] 0 0
Spain
State/province [53] 0 0
Valencia
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Bristol
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Liverpool
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00988221
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications