A Long-Term Extension Study of RoActemra/Actemra (Tocilizumab) in Patients With Juvenile Idiopathic Arthritis Who Completed WA19977 Core Study

Study Overview
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Brief Summary
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This long-term, open-label extension study will evaluate the safety of RoActemra/Actemra (tocilizumab) in patients with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 core study. Patients aged 9-18 years with at least JIA ACR30 clinical response to RoActemra/Actemra in the core study will be eligible to receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. 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 Who Completed the Global, Multinational Trial (WA19977)

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 9 to 18 years of age who completed visit 33 (week 104) of WA19977 study with at least JIA ACR30 clinical response to RoActemra/Actemra relative to baseline in WA19977, with no AEs, SAEs or conditions that lead to unacceptable risk of continued treatment Scheduled to receive first RoActemra/Actemra infusion in this study between 4 and 6 weeks after the last IV infusion in the core study Females of child-bearing potential and males with female partners of child-bearing potential must agree to use effective contraception as defined by protocol Exclusion Criteria: Patients with, according to investigator judgment, not satisfactory benefit from RoActemra/Actemra therapy within WA19977 Treatment with any investigational agent since the last administration of study drug in the core study WA19977 or current participation in another clinical trial except WA19977 Patient developed any other autoimmune rheumatic disease or overlap syndrome other than the permitted polyarticular-course JIA subsets: rheumatoid factor positive or negative JIA or extended oligoarticular JIA Patient is pregnant , lactating, or intending to become pregnant during the study and up to 12 weeks after the last administration of study drug Any significant concomitant disease or medical or surgical condition History of significant allergic or infusion reactions to prior biologic therapy Known current active acute, subacute, chronic or history of recurrent infection; patients suffering from ongoing active infections with Epstein Barr virus, herpes zoster or recurrent history of urinary tract infection can be included after the (acute) infection has been excluded or subsided Positive for latent tuberculosis (TB) Currently active asthma for which the patient has required the use of oral or parenteral corticosteroids for >/= 2 weeks within 6 months prior to entering the study Inadequate hepatic, renal or bone marrow function

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RoActemra/Actemra<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg iv every 4 weeks, 104 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events of Special Interest and Study-Drug Related Adverse Events | Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the first day of tocilizumab administration until 4 weeks after administration of the last dose of tocilizumab. AEs of special interest were Infections (including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives), Myocardial infarction/Acute coronary syndrome, Gastrointestinal perforations and related events, Malignancies, Anaphylaxis/Hypersensitivity reactions, Demyelinating disorders, Stroke. Bleeding events, Hepatic events and Macrophage activation syndrome (MAS). | Baseline and every 4 weeks up to Week 76 and Final Follow-Up Visit (up to 82 weeks) | 
| Number of AEs of Special Interest and Study Drug Related AEs | AEs and SAEs were recorded from the first day of tocilizumab administration until 4 weeks after administration of the last dose of tocilizumab. | Baseline and every 4 weeks up to Week 76 and Final Follow-Up Visit (up to 82 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90 by Visit | The six JIA ACR components comprised of: 1) Physician's global assessment of disease activity, 2) Parent/Participant's global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP), and 6) Childhood Health Assessment Questionnaire - Disease Index (CHAQ-DI). At an assessment visit, a JIA ACR30/50/70/90 response in comparison to Baseline was defined as: At least three of the six JIA ACR core components improving by at least 30 percent (%), 50%, 70%, or 90% respectively and no more than one of the remaining JIA ACR core components worsening by more than 30%. | Baseline, Weeks 12, 24, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Percentage of Participants With Inactive Disease by Visit | A participant was defined to show inactive disease if all of the following criteria were applied: 1) No joints with active arthritis (no joints with swelling and no joints with lack of motion), 2) No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, 3) No active uveitis, 4) ESR and/or CRP within normal range, and 5) Physician's global assessment of disease activity equals (=) 0 millimeters (mm) on a Visual analog scale (VAS). | Baseline, Weeks 12, 24, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Percentage of Participants Achieving Clinical Remission (CR) at Each Visit | CR was defined as clinical remission with medication (CRem). A participant was in CR if inactive disease was observed for a minimum of 6 consecutive months. | Baseline, Screening, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Visit (up to 82 weeks) | 
| Physicians Assessment of Global Activity (VAS) | The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line, score 0 represented 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end score 100 represented 'arthritis very active'. A higher score indicated more disease activity. | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Parent or Participant's Assessment of Global Activity (VAS) | The participant or parent/guardian, as appropriate, provided a rating of the participant's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line Score 0 represented 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end score 100 represented 'very poor' (ie, maximum arthritis disease activity). A higher score indicated poorer well-being. | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Number of Joints With Active Arthritis | Joints with active arthritis were defined as joints with swelling or pain and limited of motion. The maximum number of joints with active arthritis was 71.The joint assessment was performed by an independent assessor who was not the treating physician and who was blinded to all other aspects of the participant's efficacy and safety data. | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Number of Joints With Lack of Motion | Joints with lack of movement were assessed. The maximum number of joints with lack of movement was 67. The joint assessment was performed by an independent assessor who was not the treating physician and who was blinded to all other aspects of the participant's efficacy and safety data. | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) | 
| Erythrocyte Sedimentation Rate | ESR is a marker of inflammation and was measured as millimeters per hour (mm/h). Healthy individuals have low ESR. Higher ESR indicate inflammation. | Baseline, Weeks 4, 8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Visit (up to 82 weeks) | 
| CHAQ-DI Score | The CHAQ-DI questionnaire consisted of 30 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain had at least two component questions and if applicable to the participant there were four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72, and Final Follow-Up Visit (up to 82 weeks) | 
| Parent or Participant's Assessment of Pain (VAS) | Parents or participants rated participant's pain by placing a horizontal line on a VAS of 0 (no pain)- 100 mm (severe pain). | Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72, and Final Follow-Up Visit (up to 82 weeks) | 
| CRP Levels | CRP an acute phase protein, is a marker of inflammation. CRP was measured as milligrams per deciliter (mg/dL). | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Follow-Up Visit (up to 82 weeks) |