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A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00642460
First received: March 19, 2008
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: Placebo
Drug: Non-steroidal anti-inflammatory drugs (NSAIDs)
Drug: methotrexate
Drug: corticosteroids
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    Percentage of participants with ≥30% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity Visual Analog Scale (VAS), 2) Parent/Patient global assessment of overall well-being VAS, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) consisting of 30 questions in 8 domains.

    Absence of fever was defined as no diary temperature recording ≥37.5° Celsius in the preceding seven days.


  • Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline.

  • Part I, II + III: Safety: Incidence of Adverse Events [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI.

    At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%.


  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Physician's Global Assessment of disease activity is a Visual Analog Scale. The scale is 0 to 100 mm horizontal scale, the extreme left end of the line represents 'arthritis inactive' (i.e. symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. This item is completed by the treating physician.

  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The Parent/Patient global assessment of overall well-being is a VAS. The scale is a 0 to 100 mm horizontal scale, the extreme left end of the line represents 'very well' (i.e. symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (i.e. maximum arthritis disease activity). This item is completed by the patient or parent/guardian as appropriate.

  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    The maximum number of joints with active arthritis is 71 and these are defined as those in the joint assessment with: swelling present or pain present and limitation of motion.

    The joint assessment is performed by an independent assessor, who is not the treating physician, blinded to all other aspects of the patient's efficacy and safety data.


  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The maximum number of joints with limitation of movement is 67 and these are defined as those in the joint assessment with 'limitation of motion'.

  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR) is an acute phase reactant measured in mm/hour.

  • Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do).

    The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst).


  • Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Fever free was defined as no diary temperature recording ≥37.5° Celsius in the preceding fourteen days.

  • 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 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Percentage of participants with a change from an elevated hsCRP value at baseline to a normal hsCRP value at week 12; a change from anemia (low Hemoglobin) at baseline to a normal hemoglobin value at week 12; a change from thrombocytosis (elevated platelets) at baseline to a normal platelet value at week 12; a change from leukocytosis (elevated white blood cell count) at baseline to a normal white blood cell count at week 12.

  • Part I: Percentage of Participants With Concomitant Corticosteroid Reduction [ Time Frame: Week 6 or Week 8, Week 12 ] [ Designated as safety issue: No ]

    The percentage of participants receiving oral corticosteroids(CS) with a JIA ACR70 response at week 6 or Week 8 who reduced their oral CS dose by at least 20% without subsequent JIA ACR30 flare or occurrence of systemic symptoms at week 12.

    At an assessment visit a JIA ACR70 response is defined as: At least three of the six JIA ACR core components improving by at least 70% and no more than one of the remaining JIA ACR core components worsening by more than 30%.


  • Immunogenicity: Anti-tocilizumab Antibodies (HAHA) [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Concomitant Medication Reduction (Corticosteroids, Methotrexate, NSAIDs) [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Duration of Response (Inactive Disease, Clinical Remission) [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Participants rated their pain by placing a horizontal line on a Visual Analog Scale on a scale of 0 (no pain)- 100 mm (severe pain). The score at 12 weeks minus the score at baseline. A negative number indicates improvement.

  • Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    Percentage of patients who had at least a 0.13 improvement in CHAQ-DI score from Baseline to Week 12.

    The CHAQ-DI questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do).


  • Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Percentage of participants who had a rash characteristic of sJIA in the 14 days prior to the baseline visit but no rash characteristic of sJIA in the 14 days preceding the Week 12 visit day.

  • Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12 [ Time Frame: Baseline, Week 6 and Week 12 ] [ Designated as safety issue: No ]
    Part I: Percentage of patients who had anemia (hemoglobin <lower level normal based on sex and age) at Baseline and a ≥10 g/L increase in hemoglobin at Week 6 and at Week 12.

  • Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI.

    At an assessment visit a JIA ACR70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%.


  • Part II: Number of Active Joints at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    Seventy-one joints were assessed for signs of active arthritis. The mean number of joints with signs of active arthritis is reported.

  • Part II: Percentage of Participants With no Active Joints at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    Seventy-one joints were assessed for signs of active arthritis. The percentage of participants with no signs of active arthritis is reported.

  • Part II: Percentage of Participants With Inactive Disease at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]

    Criteria for Inactive Disease:

    1) No joints with active arthritis, 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal Erythrocyte Sedimentation Rate (<20 mm/hour), 4) Physician's global assessment of disease activity Visual Analog Scale (VAS) indicates no disease activity (where no disease activity is considered to be a score ≤10 mm on a 100 mm VAS).


  • Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

    Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do).

    The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst).


  • Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Percentage is based on only those participants who were on oral corticosteroid at baseline and reached a nominal visit day on which dose was calculated.

  • 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 [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]

    Rate of SAEs, Rate of Serious Infection AEs, Rate of Related SAEs (remotely, possibly, probably) to Tocilizumab (TCZ), Rate of Macrophage Activation Syndrome, Rate of AEs leading to withdrawal and Rate of deaths per 100 patient years (PY) were calculated using the formula:

    Number of Patient Events / Duration in study (years) * 100.

    Multiple occurrences of the same AE in one individual are counted.



Enrollment: 112
Study Start Date: May 2008
Estimated Study Completion Date: August 2014
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg (patients>=30kg) or 12mg/kg (patients <30kg) iv every 2 weeks. In Part III, administration frequency may be reduced to every 3 and every 4 weeks, respectively, according to an optional alternative dosing schedule.
Drug: Non-steroidal anti-inflammatory drugs (NSAIDs)
as prescribed
Drug: methotrexate
as prescribed
Drug: corticosteroids
orally, as prescribed
Placebo Comparator: 2 Drug: Placebo
iv every 2 weeks for 12 weeks
Drug: Non-steroidal anti-inflammatory drugs (NSAIDs)
as prescribed
Drug: methotrexate
as prescribed
Drug: corticosteroids
orally, as prescribed

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00642460

  Show 54 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00642460     History of Changes
Other Study ID Numbers: WA18221, 2007-000872-18
Study First Received: March 19, 2008
Results First Received: September 16, 2011
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 20, 2014