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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
Timepoint [33] 0 0
Baseline to Week 104
Secondary outcome [34] 0 0
C-reactive Protein Levels From Baseline to Week 104
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
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
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
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)
Timepoint [38] 0 0
Baseline to Week 104
Secondary outcome [39] 0 0
Oral Corticosteroid Dose at Baseline, Week 52, and Week 104
Timepoint [39] 0 0
Baseline to Week 104
Secondary outcome [40] 0 0
Methotrexate Dose at Baseline, Week 52, and Week 104
Timepoint [40] 0 0
Baseline to Week 104
Secondary outcome [41] 0 0
Height Standard Deviation Score at Baseline, Week 52, and Week 104
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
Sex
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
30/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/01/2013
Sample size
Target
Accrual to date
Final
188
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/study/NCT00988221
Trial related presentations / publications
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.
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.
Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Perez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gamir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F; Paediatric Rheumatology International Trials Organisation PRINTO; Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00988221