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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00988221
First received: October 1, 2009
Last updated: September 5, 2013
Last verified: December 2012

October 1, 2009
September 5, 2013
November 2009
January 2013   (final data collection date for primary outcome measure)
Percentage of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40) [ Time Frame: Week 16 through Week 40 ] [ Designated as safety issue: No ]
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 using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
Proportion of patients with a JIA ACR30 flare in Part II (tocilizumab versus placebo) [ Time Frame: weeks 16-40 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00988221 on ClinicalTrials.gov Archive Site
  • Percentage 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 (Weeks 0-16) [ Time Frame: Week 0 through Week 16 ] [ Designated as safety issue: No ]
    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 using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    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.
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    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.
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    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.
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    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.
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
  • Percentage Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    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 is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.
  • Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    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 scores for the first 3 components range from 0-10; the score for the final component ranges from 0-27. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.
  • Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    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.
  • Percentage of Patients With Inactive Disease at the End of Part I of the Study (Week 16) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    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 patient/parent's global assessment of overall well-being visual analog scale score ≤ 10.
  • Percentage of Patients With an Elevated C-reactive Protein Concentration at Baseline (Week 0) That Had Normalized at the End of Part I of the Study (Week 16) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.
  • Percentage of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline (Week 0) That Had Normalized at the End of Part I of the Study (Week 16) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.
  • Percentage of Patients With an Elevated Platelet Count at Baseline (Week 0) That Had Normalized at the End of Part I of the Study (Week 16) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    Platelets were measured in blood samples taken from the patients.
  • Percentage of Patients With an Elevated White Blood Count at Baseline (Week 0) That Had Normalized at the End of Part I of the Study (Week 16) [ Time Frame: Baseline (Week 0) to Week 16 ] [ Designated as safety issue: No ]
    White blood cells were measured in blood samples taken from the patients.
  • Percentage 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) [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    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 using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).
  • Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline (Week 0) 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) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.
  • Change From Baseline (Week 0) in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part II of the Study (Week 40) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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 is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.
  • Change From Baseline (Week 0) in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40) [ Time Frame: Baseline (Week 0) to Week 40 ] [ Designated as safety issue: No ]
    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. A negative change score indicates improvement.
  • Percentage of Patients With Inactive Disease at the End of Part II of the Study (Week 40) [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    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 patient/parent's global assessment of overall well-being visual analog scale score ≤ 10.
  • Efficacy Part I: JIA ACR Core Set Variables [ Time Frame: assessed at weeks 2,4,8,12 and 16 ] [ Designated as safety issue: No ]
  • Long-term effect and maintenance of clinical response (Part III): JIA ACR Core Set Variables [ Time Frame: assessed every 4 weeks up to week 104 ] [ Designated as safety issue: No ]
  • Safety and tolerability: AEs, laboratory parameters [ Time Frame: throughout study, laboratory assessments every 4 weeks ] [ Designated as safety issue: No ]
  • efficacy/safety of 8mg/kg versus 10mg/kg in patients <30kg (Part I, II and III) [ Time Frame: throughout study, clinical and laboratory assessments every 4 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Tocilizumab in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis
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.

This 3-part study will evaluate 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 will receive iv infusions of tocilizumab (8mg/kg for patients >/=30kg, 8mg/kg or 10mg/kg for patients <30kg) every 4 weeks for 16 weeks. For Part II, patients with an adequate response in Part I will be 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 will receive 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 NSAIDs, corticosteroids or methotrexate will continue throughout the study. Anticipated time on study treatment is 2 years, and target sample size is 150-200 individuals.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Juvenile Idiopathic Arthritis
  • Drug: tocilizumab [RoActemra/Actemra]
    8mg/kg or 10mg/kg iv infusion every 4 weeks, 16 weeks
  • Drug: tocilizumab [RoActemra/Actemra]
    8mg/kg or 10mg/kg iv infusion every 4 weeks, 24 weeks
  • Drug: tocilizumab [RoActemra/Actemra]
    8mg/kg or 10 mg/kg iv infusion every 4 weeks, 64 weeks
  • Drug: placebo
    iv infusion every 4 weeks, 24 weeks
  • Drug: NSAIDs, corticosteroids, methotrexate
    as prescribed
  • Active Comparator: I
    Interventions:
    • Drug: tocilizumab [RoActemra/Actemra]
    • Drug: NSAIDs, corticosteroids, methotrexate
  • Experimental: IIA
    Interventions:
    • Drug: tocilizumab [RoActemra/Actemra]
    • Drug: NSAIDs, corticosteroids, methotrexate
  • Placebo Comparator: IIB
    Interventions:
    • Drug: placebo
    • Drug: NSAIDs, corticosteroids, methotrexate
  • Active Comparator: III
    Interventions:
    • Drug: tocilizumab [RoActemra/Actemra]
    • Drug: NSAIDs, corticosteroids, methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
188
January 2013
January 2013   (final data collection date for primary outcome measure)

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 NSAIDs 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

Exclusion Criteria:

  • auto-immune, rheumatic disease or overlap syndrome other than polyarticular-course JIA
  • wheelchair bound or bedridden
  • intraarticular, intramuscular, intravenous or long-acting corticosteroids within 4 weeks prior to baseline
  • DMARDs (other than methotrexate) within 4 weeks prior to baseline
  • previous treatment with tocilizumab
Both
2 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Brazil,   Canada,   France,   Germany,   Italy,   Mexico,   Peru,   Poland,   Russian Federation,   Spain,   United Kingdom
 
NCT00988221
WA19977, 2009-011593-15
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP