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

March 19, 2008
December 18, 2012
May 2008
September 2009   (final data collection date for primary outcome measure)
  • 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 ]
Proportion of patients with >=30% improvement in JIA core set and absence of fever [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00642460 on ClinicalTrials.gov Archive Site
  • 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.

  • % patients with 30/50/70/90% improvement in JIA core set; reduction in steroid use; change in individual components of JIA core set; change in hsCRP, anemia, platelet count, total WBC, incidence of rash;improvement in CHAQ, and VAS [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Time from baseline to achievement of JIA ACR 30/50/70/90 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • AEs, lab parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Juvenile Idiopathic Arthritis
  • 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: 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
  • Experimental: 1
    Interventions:
    • Drug: tocilizumab [RoActemra/Actemra]
    • Drug: Non-steroidal anti-inflammatory drugs (NSAIDs)
    • Drug: methotrexate
    • Drug: corticosteroids
  • Placebo Comparator: 2
    Interventions:
    • Drug: Placebo
    • Drug: Non-steroidal anti-inflammatory drugs (NSAIDs)
    • Drug: methotrexate
    • Drug: corticosteroids
De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A; PRINTO; PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2385-95. doi: 10.1056/NEJMoa1112802.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
112
August 2014
September 2009   (final data collection date for primary outcome measure)

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
Both
2 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   United States,   United Kingdom,   Australia,   Belgium,   Brazil,   Canada,   Czech Republic,   Denmark,   Germany,   Greece,   Italy,   Mexico,   Netherlands,   Norway,   Poland,   Slovakia,   Spain,   Sweden
 
NCT00642460
WA18221, 2007-000872-18
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