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NCT00988221

A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Completed Phase 3 Results posted Last updated 26 July 2017
What this trial tests

Phase 3 trial testing Tocilizumab in Juvenile Idiopathic Arthritis in 188 participants. Completed in 28 January 2013.

Timeline
30 November 2009
Primary endpoint
30 November 2011
28 January 2013

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment188
Start date30 November 2009
Primary completion30 November 2011
Estimated completion28 January 2013
Sites69 locations across France, Italy, Russia, Peru, Belgium, United Kingdom, Germany, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 2 to 17, any sex, with Juvenile Idiopathic Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Week 16 through Week 40

JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving \> 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed

GroupValue95% CI
Placebo48.137.0 – 59.0
Tocilizumab 8 or 10 mg/kg25.616.0 – 35.0
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) Secondary · Baseline to Week 16

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening \> 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed usi

ACR30 response
GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg88.6
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg76.5
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg93.3
Tocilizumab 8 or 10 mg/kg89.4
ACR50 response
GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg80.0
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg70.6
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg87.4
Tocilizumab 8 or 10 mg/kg83.0
ACR70 response
GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg62.9
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg41.2
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg68.1
Tocilizumab 8 or 10 mg/kg62.2
ACR90 response
GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg31.4
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg23.5
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg25.2
Tocilizumab 8 or 10 mg/kg26.1
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) Secondary · Baseline to Week 16

The patient's treating physician provides a rating of the patient'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.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-61.48± 48.779
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-65.20± 26.170
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-72.61± 25.977
Tocilizumab 8 or 10 mg/kg-69.19± 31.824
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) Secondary · Baseline to Week 16

The patient or parent/guardian, as appropriate, provides a rating of the patient'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.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-31.65± 120.268
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-55.56± 42.092
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-53.34± 58.686
Tocilizumab 8 or 10 mg/kg-49.46± 72.920
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) Secondary · Baseline to Week 16

Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-63.36± 43.272
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-55.57± 44.876
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-72.96± 33.915
Tocilizumab 8 or 10 mg/kg-68.15± 38.246
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) Secondary · Baseline to Week 16

Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-61.83± 34.726
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-49.87± 48.091
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-65.96± 30.134
Tocilizumab 8 or 10 mg/kg-62.42± 34.955
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) Secondary · Baseline to Week 16

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-70.98± 24.530
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-21.84± 159.592
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-70.87± 33.400
Tocilizumab 8 or 10 mg/kg-62.54± 73.384
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) Secondary · Baseline to Week 16

Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which 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. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg-54.48± 37.214
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg-46.16± 50.961
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg-49.07± 45.048
Tocilizumab 8 or 10 mg/kg-49.62± 44.573
Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16) Secondary · Week 16

The JADAS-27 is derived from the following components: Physician's global assessment of disease activity on a 0-100 mm visual analog scale (VAS)/10, patient/parent's global assessment of overall well-being on a 0-100 mm VAS/10, normalized erythrocyte sedimentation rate (ESR) (if ESR is ≤ 20 then set to 0, if ≥ 120 then set to 10, and if \> 20 and \< 120 then apply formula \[ESR-20\]/10), and number of joints (maximum of 27) with active arthritis (cervical spine, left/right elbow, left/right wrist, left/right MCP1-3, left/right PIP1-5, left/right hips, left/right knee and left/right ankle). The

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg9.08± 8.882
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg12.25± 10.277
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg7.83± 7.122
Tocilizumab 8 or 10 mg/kg8.82± 8.198
Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16) Secondary · Week 16

The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg21.9± 21.66
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg24.1± 23.94
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg20.3± 21.13
Tocilizumab 8 or 10 mg/kg21.2± 21.65
Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16) Secondary · Week 16

A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (\< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg20.0
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg8.8
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg18.5
Tocilizumab 8 or 10 mg/kg17.0
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) Secondary · Baseline to Week 16

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

GroupValue95% CI
Tocilizumab 10 mg/kg in Patients Weighing < 30 kg76.9
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg63.2
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg87.0
Tocilizumab 8 or 10 mg/kg79.5

Adverse events — posted to ClinicalTrials.gov

Time frame: All exposure safety population: All participants randomized into Part I of the study who received at least 1 infusion of tocilizumab and had at least 1 post-baseline safety assessment or event.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tocilizumab 10 mg/kg in Patients Weighing < 30 kg
Serious: 4/22 (18%)
Deaths:
Tocilizumab 10 mg/kg to 8 mg/kg in Patients Weighing < 30 kg
Serious: 1/13 (8%)
Deaths:
Tocilizumab 8 mg/kg in Patients Weighing < 30 kg
Serious: 4/34 (12%)
Deaths:
Tocilizumab 8 mg/kg in Patients Weighing ≥ 30 kg
Serious: 17/119 (14%)
Deaths:
All Tocilizumab Patients
Serious: 26/188 (14%)
Deaths:

Serious adverse events (26 terms)

ReactionSystemTocilizumab 10 mg/kg in Pa…Tocilizumab 10 mg/kg to 8 …Tocilizumab 8 mg/kg in Pat…Tocilizumab 8 mg/kg in Pat…All Tocilizumab Patients
PneumoniaInfections and infestations
BronchitisInfections and infestations
CellulitisInfections and infestations
VaricellaInfections and infestations
UveitisEye disorders
Neck injuryInjury, poisoning and procedural complications
Synovial ruptureInjury, poisoning and procedural complications
Upper limb fractureInjury, poisoning and procedural complications
Cholangitis sclerosingHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Back painMusculoskeletal and connective tissue disorders
OsteoporosisMusculoskeletal and connective tissue disorders
Familial mediterranean feverCongenital, familial and genetic disorders
ConstipationGastrointestinal disorders
Benign intracranial hypertensionNervous system disorders
Psychosomatic diseasePsychiatric disorders
Calculus urinaryRenal and urinary disorders
AppendicitisInfections and infestations
Epstein-Barr Virus InfectionInfections and infestations
ParonychiaInfections and infestations
PyelonephritisInfections and infestations
TonsillitisInfections and infestations
Viral infectionInfections and infestations
SclerodermaMusculoskeletal and connective tissue disorders
PregnancyPregnancy, puerperium and perinatal conditions
Other adverse events (72 terms — click to expand)

ReactionSystemTocilizumab 10 mg/kg in Pa…Tocilizumab 10 mg/kg to 8 …Tocilizumab 8 mg/kg in Pat…Tocilizumab 8 mg/kg in Pat…All Tocilizumab Patients
Juvenile arthritisMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
PharyngitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
RhinitisInfections and infestations
Ear infectionInfections and infestations
RashSkin and subcutaneous tissue disorders
GastroenteritisInfections and infestations
InfluenzaInfections and infestations
SinusitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal pain upperGastrointestinal disorders
ConjunctivitisEye disorders
BronchitisInfections and infestations
Urinary tract infectionInfections and infestations
EpistaxisRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Ear painEar and labyrinth disorders
Oral herpesInfections and infestations
PharyngotonsillitisInfections and infestations
Mouth ulcerationGastrointestinal disorders
Ligament sprainInjury, poisoning and procedural complications
PyrexiaGeneral disorders
RhinorrhoeaRenal and urinary disorders
Ingrowing nailSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
Arthropod biteInjury, poisoning and procedural complications
Otitis mediaInfections and infestations
PneumoniaInfections and infestations
Respiratory tract infection viralInfections and infestations
Aphthous stomatitisGastrointestinal disorders
EczemaSkin and subcutaneous tissue disorders
Transaminases increasedInvestigations

Most-reported serious reactions: Pneumonia, Bronchitis, Cellulitis, Varicella, Uveitis, Neck injury, Synovial rupture, Upper limb fracture.

Data from ClinicalTrials.gov NCT00988221 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial.
    Brunner HI, Ruperto N, Zuber Z, Keane C, et al · · 2015 · cited 190× · PMID 24834925 · DOI 10.1136/annrheumdis-2014-205351
  2. Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial.
    Brunner HI, Ruperto N, Zuber Z, Cuttica R, et al · · 2021 · cited 32× · PMID 32951358 · DOI 10.1002/art.41528
  3. Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology - what we know and what we do not know from randomized controlled trials.
    Welzel T, Winskill C, Zhang N, Woerner A, et al · · 2021 · cited 19× · PMID 33766063 · DOI 10.1186/s12969-021-00514-4
  4. Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials.
    Malattia C, Ruperto N, Pederzoli S, Palmisani E, et al · · 2020 · cited 11× · PMID 32912276 · DOI 10.1186/s13075-020-02303-y
  5. Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis.
    Pardeo M, Wang J, Ruperto N, Alexeeva E, et al · · 2019 · cited 11× · PMID 30824645 · DOI 10.3899/jrheum.180795
  6. Functional Ability and Health-Related Quality of Life in Randomized Controlled Trials of Tocilizumab in Patients With Juvenile Idiopathic Arthritis.
    Brunner HI, Chen C, Bovis F, De Benedetti F, et al · · 2021 · cited 10× · PMID 32702212 · DOI 10.1002/acr.24384
  7. Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.
    Schanberg LE, Mulugeta LY, Akinlade B, Brunner HI, et al · · 2023 · cited 7× · PMID 37067688 · DOI 10.1002/art.42534
  8. Value of Literature Review to Inform Development and Use of Biologics in Juvenile Idiopathic Arthritis.
    Golhen K, Winskill C, Yeh C, Zhang N, et al · · 2022 · cited 4× · PMID 35799700 · DOI 10.3389/fped.2022.909118

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Other trials of Tocilizumab

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00988221.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing