Overview

This trial is active, not recruiting.

Condition juvenile idiopathic arthritis
Treatments tocilizumab [roactemra/actemra], placebo, non-steroidal anti-inflammatory drugs (nsaids), methotrexate, corticosteroids
Phase phase 3
Sponsor Hoffmann-La Roche
Start date May 2008
End date September 2009
Trial size 112 participants
Trial identifier NCT00642460, 2007-000872-18, WA18221

Summary

This study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active systemic juvenile idiopathic arthritis (sJIA) who have an inadequate clinical response to NSAIDs and corticosteroids. In Part I of the study patients will be randomized 2:1 to receive iv infusions of RoActemra/Actemra (8mg/kg iv for patients >=30kg, or 12mg/kg for patients <30kg) or placebo, every 2 weeks. Stable NSAIDs and methotrexate will be continued throughout. After 12 weeks of double-blind treatment, all patients will have the option to enter Part II of the study to receive open-label treatment with RoActemra/Actemra for a further 92 weeks, followed by a 3-year continuation of the study in Part III in which, for patients who meet specific criteria, an optional alternative dosing schedule decreasing the study drug administration frequency will be introduced. Anticipated time on study treatment is up to 5 years.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
tocilizumab [roactemra/actemra]
8mg/kg (patients>=30kg) or 12mg/kg (patients <30kg) iv every 2 weeks. In Part III, administration frequency may be reduced to every 3 and every 4 weeks, respectively, according to an optional alternative dosing schedule.
non-steroidal anti-inflammatory drugs (nsaids)
as prescribed
methotrexate
as prescribed
corticosteroids
orally, as prescribed
(Placebo Comparator)
placebo
iv every 2 weeks for 12 weeks
non-steroidal anti-inflammatory drugs (nsaids)
as prescribed
methotrexate
as prescribed
corticosteroids
orally, as prescribed

Primary Outcomes

Measure
Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever
time frame: Baseline, Week 12
Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104
time frame: Baseline, Week 104
Part I, II + III: Safety: Incidence of Adverse Events
time frame: 260 weeks

Secondary Outcomes

Measure
Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate
time frame: Baseline, Week 12
Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)
time frame: Baseline, Week 12
Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12
time frame: Baseline, Week 12
Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein(hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12
time frame: Baseline, Week 12
Part I: Percentage of Participants With Concomitant Corticosteroid Reduction
time frame: Week 6 or Week 8, Week 12
Immunogenicity: Anti-tocilizumab Antibodies (HAHA)
time frame: 260 weeks
Concomitant Medication Reduction (Corticosteroids, Methotrexate, NSAIDs)
time frame: 260 weeks
Duration of Response (Inactive Disease, Clinical Remission)
time frame: 260 weeks
Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12
time frame: Baseline, Week 12
Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12
time frame: Baseline, Week 12
Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12
time frame: Baseline, Week 12
Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12
time frame: Baseline, Week 6 and Week 12
Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104
time frame: Baseline, Week 104
Part II: Number of Active Joints at Week 104
time frame: Week 104
Part II: Percentage of Participants With no Active Joints at Week 104
time frame: Week 104
Part II: Percentage of Participants With Inactive Disease at Week 104
time frame: Week 104
Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104
time frame: Baseline, Week 104
Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104
time frame: Baseline, Week 104
Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104
time frame: 104 Weeks

Eligibility Criteria

Male or female participants from 2 years up to 17 years old.

Inclusion Criteria: - Patients aged 2-17 years of age - Systemic juvenile idiopathic arthritis with >= 6 months persistent activity - Presence of active disease (>=5 active joints, or >=2 active joints + fever + steroids) - Inadequate clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids due to toxicity or lack of efficacy Exclusion Criteria: - Wheelchair-bound or bed-ridden - Any other autoimmune, rheumatic disease or overlap syndrome other than systemic juvenile idiopathic arthritis - Intravenous long-acting corticosteroids or intra-articular corticosteroids within 4 weeks of baseline, or throughout study - Disease-modifying antirheumatic drugs (DMARDs), other than methotrexate - Previous treatment with tocilizumab

Additional Information

Official title A Randomized, Placebo-controlled Study to Evaluate the Effect of Tocilizumab on Disease Response in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA), With an Open-label Extension to Examine the Long Term Use of Tocilizumab
Trial information was received from ClinicalTrials.gov and was last updated in December 2012.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.