Clinical trial NCT00642460: A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-03-25
Enrollment: 112
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

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
timeFrame: Baseline, Week 12
measure: Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104
timeFrame: Baseline, Week 104
Secondary outcomes:
measure: Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate
timeFrame: Baseline, Week 12
measure: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)
timeFrame: Baseline, Week 12
measure: Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12
timeFrame: Baseline, Week 12
measure: 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
timeFrame: Baseline, Week 12
measure: Part I: Percentage of Participants With Concomitant Corticosteroid Reduction
timeFrame: Week 6 or Week 8, Week 12
measure: Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12
timeFrame: Baseline, Week 12
measure: Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12
timeFrame: Baseline, Week 12
measure: Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12
timeFrame: Baseline, Week 12
measure: Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12
timeFrame: Baseline, Week 6 and Week 12
measure: Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104
timeFrame: Baseline, Week 104
measure: Part II: Number of Active Joints at Week 104
timeFrame: Week 104
measure: Part II: Percentage of Participants With no Active Joints at Week 104
timeFrame: Week 104
measure: Part II: Percentage of Participants With Inactive Disease at Week 104
timeFrame: Week 104
measure: Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104
timeFrame: Baseline, Week 104
measure: Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104
timeFrame: Baseline, Week 104
measure: 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
timeFrame: 104 Weeks
measure: Part III: Percentage of Participants With at Least 30%, 50%, 70%, and 90% Improvement in JIA Core Set According to ACR
timeFrame: Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
measure: Part III: Percentage of Participants Who Maintain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 Response for 6 Months Previous to the Specified Week
timeFrame: Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
measure: Part III: Doses of Oral Corticosteroids
timeFrame: Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
measure: Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
timeFrame: Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
measure: Part III: Percentage of Participants With a >=20/50/75/90% Decrease From Baseline in Oral Corticosteroid Dose at Visits
timeFrame: Every 2 weeks from Week 104 to Week 260
measure: Part III: Percentage of Participants With Inactive Disease
timeFrame: Weeks 104, 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
measure: Part III: Percentage of Participants in Clinical Remission
timeFrame: Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
measure: Part III: Percentage of Participants on Corticosteroids at Baseline in Clinical Remission Off All Oral Corticosteroids for 6 Months Prior to Specified Visits
timeFrame: Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
measure: Part III: Percentage of Participants on Methotrexate At Baseline in Clinical Remission Off Corticosteroids and Methotrexate for 6 Months Prior to Specified Visits
timeFrame: Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
measure: Part III: Percentage of Participants in Clinical Remission Off All Arthritis Medications Except Tocilizumab for 6 Months Prior to Specified Visits
timeFrame: Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
measure: Part III: Percentage of Participants Who Developed Antibodies To Tocilizumab During Weeks 104 to 260
timeFrame: Every 2 weeks from Week 104 to 260
measure: Part III: Percentage of Participants Who Developed Anti-TCZ Antibodies Associated With The Occurrence of Drug Hypersensitivity Reactions.
timeFrame: Every 2 weeks from Week 104 to 260
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Hackensack
country: United States
state: New Jersey
city: Livingston
country: United States
state: New Jersey
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Houston
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: La Plata
country: Argentina
city: Parkville
country: Australia
city: Subiaco
country: Australia
city: Westmead
country: Australia
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Praha
country: Czech Republic
city: Copenhagen
country: Denmark
city: Berlin
country: Germany
city: Bremen
country: Germany
city: Sankt Augustin
country: Germany
city: Athens
country: Greece
city: Heraklion
country: Greece
city: Ioannina
country: Greece
city: Genova
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Roma
country: Italy
city: Mexico
country: Mexico
city: Miexico City
country: Mexico
city: Utrecht
country: Netherlands
city: Oslo
country: Norway
city: Kraków
country: Poland
city: Lublin
country: Poland
city: Piestany
country: Slovakia
city: Barcelona
country: Spain
city: Esplugas de Llobregat
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Goeteborg
country: Sweden
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Malattia C, Ruperto N, Pederzoli S, Palmisani E, Pistorio A, Wouters C, Dolezalova P, Flato B, Garay S, Giancane G, Wells C, Douglass W, Brunner HI, De Benedetti F, Ravelli A; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials. Arthritis Res Ther. 2020 Sep 10;22(1):211. doi: 10.1186/s13075-020-02303-y.
citation: Pardeo M, Wang J, Ruperto N, Alexeeva E, Chasnyk V, Schneider R, Horneff G, Huppertz HI, Minden K, Onel K, Zemel L, Martin A, Kone-Paut I, Siamopoulou-Mavridou A, Silva CA, Porter-Brown B, Bharucha KN, Brunner HI, De Benedetti F; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis. J Rheumatol. 2019 Sep;46(9):1117-1126. doi: 10.3899/jrheum.180795. Epub 2019 Mar 1.
citation: De Benedetti F, Brunner H, Ruperto N, Schneider R, Xavier R, Allen R, Brown DE, Chaitow J, Pardeo M, Espada G, Gerloni V, Myones BL, Frane JW, Wang J, Lipman TH, Bharucha KN, Martini A, Lovell D; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group. Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: results from a phase III trial. Arthritis Rheumatol. 2015 Mar;67(3):840-8. doi: 10.1002/art.38984.
citation: De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A; PRINTO; PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2385-95. doi: 10.1056/NEJMoa1112802.