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
  Purpose

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.


Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: placebo
Drug: NSAIDs, corticosteroids, methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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]).


Secondary Outcome Measures:
  • 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.


Enrollment: 188
Study Start Date: November 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: I Drug: tocilizumab [RoActemra/Actemra]
8mg/kg or 10mg/kg iv infusion every 4 weeks, 16 weeks
Drug: NSAIDs, corticosteroids, methotrexate
as prescribed
Experimental: IIA Drug: tocilizumab [RoActemra/Actemra]
8mg/kg or 10mg/kg iv infusion every 4 weeks, 24 weeks
Drug: NSAIDs, corticosteroids, methotrexate
as prescribed
Placebo Comparator: IIB Drug: placebo
iv infusion every 4 weeks, 24 weeks
Drug: NSAIDs, corticosteroids, methotrexate
as prescribed
Active Comparator: III Drug: tocilizumab [RoActemra/Actemra]
8mg/kg or 10 mg/kg iv infusion every 4 weeks, 64 weeks
Drug: NSAIDs, corticosteroids, methotrexate
as prescribed

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00988221

  Show 69 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00988221     History of Changes
Other Study ID Numbers: WA19977, 2009-011593-15
Study First Received: October 1, 2009
Results First Received: August 29, 2012
Last Updated: September 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Arthritis, Rheumatoid
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Methotrexate
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on April 22, 2014