An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis

Study Overview
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Brief Summary
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This long-term, interventional, open-label extension study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients from Poland and Russia with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 study. Patients will receive RoActemra/Actemra 8 mg/kg every 4 weeks. The anticipated time on study treatment is 104 weeks.

Official Title
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Long-term, Interventional, Open Label Extension Study Evaluating the Safety of Tocilizumab Treatment in Patients With Polyarticular-course Juvenile Idiopathic Arthritis From Poland and Russia Who Completed the Global, Multinational Trial (WA19977).

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: RoActemra/Actemra (tocilizumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who completed 104 weeks of study WA19977 with at least a JIA ACR30 clinical response to RoActemra/Actemra and no serious adverse event or adverse event Written informed consent obtained from patient if patient is 18 years of age and older, or if under the age of 18 years from parents or legal guardian Exclusion Criteria: Patient did not benefit from RoActemra/Actemra therapy in study WA19977 Treatment with any investigational drug since the last administration of study drug in the core study WA19977 Patients developed any other autoimmune rheumatic disease other than the permitted JIA subsets Any significant medical or surgical condition that would jeopardize patient's safety Current serious uncontrolled concomitant disease or infection

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RoActemra/Actemra (tocilizumab)<br>* Tocilizumab 8 mg/kg every 4 weeks for 104 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) | AE: unfavorable and unintended sign, symptom, or disease associated with use of treatment, regardless of treatment relation. Pre-existing conditions that worsened and laboratory or clinical tests that resulted in change in treatment or discontinuation from treatment were reported as AEs. Serious AE: resulted in death, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically significant. Severe AE: AE that caused inability to work or perform normal daily activity. AEs of special interest: Serious infections (including opportunistic infections), Myocardial infarction/Acute coronary syndrome, Gastrointestinal perforations and related AE, Malignant neoplasms, Anaphylaxis event, Demyelination-related events, Stroke, Spontaneous or serious bleeding, Serious/medically significant hepatic events. Any AE included serious and non-serious AE. | Baseline to 12 weeks after last actual study medication (up to 101 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With JIA ACR 30 Response at Weeks 12, 24 and End of Follow Up | JIA ACR30 response was defined as 3 of any 6 core outcome variables improved by at least 30% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: Physician global assessment (PGA) of disease activity using Visual Analog Scale (VAS) from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); Patient/parent global assessment (PtGA) of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and Erythrocyte Sedimentation Rate (ESR). | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Percentage of Participants With JIA ACR 50 Response at Weeks 12, 24 and End of Follow up | JIA ACR50 response was defined as 3 of any 6 core outcome variables improved by at least 50% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR. | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Percentage of Participants With JIA ACR 70 Response at Weeks 12, 24 and End of Follow up | JIA ACR70 response was defined as 3 of any 6 core outcome variables improved by at least 70% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Percentage of Participants With JIA ACR 90 Response at Weeks 12, 24 and End of Follow up | JIA ACR90 response was defined as 3 of any 6 core outcome variables improved by at least 90% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR. | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Percentage of Participants With Inactive Disease at Week 12, 24 and End of Follow up | Criteria for Inactive Disease: 1) No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both), 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal ESR (less than [<] 20 millimeters per hour [mm/hour]), and 4) PGA of disease activity using VAS indicated no disease activity (where no disease activity is considered to be a score less than or equal to [≤]10 mm on a 100 mm VAS where left end of line 0 [inactive arthritis] to right end of line 100 [very active arthritis]). | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Percentage of Participants With Clinical Remission at Week 12, 24 and End of Follow up | Clinical remission: inactive disease for minimum of 6 continuous months while on medication (Level 1); off oral corticosteroid medications but still on tocilizumab (Level 2); off both methotrexate and oral corticosteroids but still on tocilizumab (Level 3); or off all anti-arthritis medications-oral corticosteroids, methotrexate, non-steroidal anti-inflammatory drugs but still on tocilizumab (Level 4). Inactive disease: No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to sJIA; Normal ESR (<20 mm/hour); PGA of disease activity indicated no disease activity (score ≤10 mm on a 100 mm VAS where 0 [inactive arthritis] and 100 [very active arthritis]). Overall percentage of participants with clinical remission (any level) are reported. | Baseline, Week 12, 24, End of Follow up (up to 101 weeks) | 
| Change From Baseline in Joints With Active Arthritis at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up | Joint with active arthritis was defined as a joint with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in Number of Joints With Limitation of Movement at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up | The maximum number of joints with limitation of movement is 67 and these were defined as those with 'limitation of motion'. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in PGA of Disease Activity at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up | The physician provides a rating of the participant'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. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in PtGA of Overall Well-Being at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up | The participant or parent/guardian, as appropriate, provides a rating of the participant'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. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in ESR at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up |  | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in Childhood Health Assessment - Disability Index (CHAQ-DI) at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up | The 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 participant 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. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Percentage of Participants With Minimally Important Improvement in the CHAQ-DI Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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 participant 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 minimally important improvement was defined as at least a 0.13 improvement in CHAQ-DI score from baseline. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Activitiy) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Activity component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Arising) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Arising component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Dressing and Grooming) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Dressing and Grooming component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Eating) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Eating component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Grip) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Grip component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Hygiene) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Hygiene component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Reach) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Reach component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Change From Baseline in CHAQ-DI (Walking) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up | The 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. Walking component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) | 
| Absolute C-Reactive Protein Levels |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, End of follow up (up to 101 weeks) |