A Long-Term Extension Study of RoActemra/Actemra (Tocilizumab) in Patients With Juvenile Idiopathic Arthritis Who Completed WA19977 Core Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01667471
First received: August 15, 2012
Last updated: February 1, 2016
Last verified: February 2016
  Purpose
This long-term, open-label extension study will evaluate the safety of RoActemra/Actemra (tocilizumab) in patients with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 core study. Patients aged 9-18 years with at least JIA ACR30 clinical response to RoActemra/Actemra in the core study will be eligible to receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. Anticipated time on study treatment is 104 weeks.

Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-term, Interventional, Open Label Extension Study Evaluating the Safety of Tocilizumab Treatment in Patients With Polyarticular-course Juvenile Idiopathic Arthritis Who Completed the Global, Multinational Trial (WA19977)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With Adverse Events of Special Interest and Study-Drug Related Adverse Events [ Time Frame: Baseline and every 4 weeks up to Week 76 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the first day of tocilizumab administration until 4 weeks after administration of the last dose of tocilizumab. AEs of special interest were Infections (including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives), Myocardial infarction/Acute coronary syndrome, Gastrointestinal perforations and related events, Malignancies, Anaphylaxis/Hypersensitivity reactions, Demyelinating disorders, Stroke. Bleeding events, Hepatic events and Macrophage activation syndrome (MAS).

  • Number of AEs of Special Interest and Study Drug Related AEs [ Time Frame: Baseline and every 4 weeks up to Week 76 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    AEs and SAEs were recorded from the first day of tocilizumab administration until 4 weeks after administration of the last dose of tocilizumab.


Secondary Outcome Measures:
  • Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90 by Visit [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]

    The six JIA ACR components comprised of: 1) Physician's global assessment of disease activity, 2) Parent/Participant's 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 (ESR) and/or C-reactive Protein (CRP), and 6) Childhood Health Assessment Questionnaire - Disease Index (CHAQ-DI).

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


  • Percentage of Participants With Inactive Disease by Visit [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    A participant was defined to show inactive disease if all of the following criteria were applied: 1) No joints with active arthritis (no joints with swelling and no joints with lack of motion), 2) No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, 3) No active uveitis, 4) ESR and/or CRP within normal range, and 5) Physician's global assessment of disease activity equals (=) 0 millimeters (mm) on a Visual analog scale (VAS).

  • Percentage of Participants Achieving Clinical Remission (CR) at Each Visit [ Time Frame: Baseline, Screening, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    CR was defined as "clinical remission with medication (CRem)". A participant was in CR if inactive disease was observed for a minimum of 6 consecutive months.

  • Physicians Assessment of Global Activity (VAS) [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line, score 0 represented 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end score 100 represented 'arthritis very active'. A higher score indicated more disease activity.

  • Parent or Participant's Assessment of Global Activity (VAS) [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    The participant or parent/guardian, as appropriate, provided a rating of the participant's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line Score 0 represented 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end score 100 represented 'very poor' (ie, maximum arthritis disease activity). A higher score indicated poorer well-being.

  • Number of Joints With Active Arthritis [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    Joints with active arthritis were defined as joints with swelling or pain and limited of motion. The maximum number of joints with active arthritis was 71.The joint assessment was performed by an independent assessor who was not the treating physician and who was blinded to all other aspects of the participant's efficacy and safety data.

  • Number of Joints With Lack of Motion [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    Joints with lack of movement were assessed. The maximum number of joints with lack of movement was 67. The joint assessment was performed by an independent assessor who was not the treating physician and who was blinded to all other aspects of the participant's efficacy and safety data.

  • Erythrocyte Sedimentation Rate [ Time Frame: Baseline, Weeks 4, 8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    ESR is a marker of inflammation and was measured as millimeters per hour (mm/h). Healthy individuals have low ESR. Higher ESR indicate inflammation.

  • CHAQ-DI Score [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72, and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI questionnaire consisted of 30 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain had at least two component questions and if applicable to the participant there were 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).

  • Parent or Participant's Assessment of Pain (VAS) [ Time Frame: Baseline, Weeks 12, 24, 28, 32, 36, 48, 60, 72, and Final Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    Parents or participants rated participant's pain by placing a horizontal line on a VAS of 0 (no pain)- 100 mm (severe pain).

  • CRP Levels [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76 and Final Follow-Up Follow-Up Visit (up to 82 weeks) ] [ Designated as safety issue: No ]
    CRP an acute phase protein, is a marker of inflammation. CRP was measured as milligrams per deciliter (mg/dL).


Enrollment: 6
Study Start Date: January 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RoActemra/Actemra Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, 104 weeks

  Eligibility

Ages Eligible for Study:   9 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 9 to 18 years of age who completed visit 33 (week 104) of WA19977 study with at least JIA ACR30 clinical response to RoActemra/Actemra relative to baseline in WA19977, with no AEs, SAEs or conditions that lead to unacceptable risk of continued treatment
  • Scheduled to receive first RoActemra/Actemra infusion in this study between 4 and 6 weeks after the last IV infusion in the core study
  • Females of child-bearing potential and males with female partners of child-bearing potential must agree to use effective contraception as defined by protocol

Exclusion Criteria:

  • Patients with, according to investigator judgment, not satisfactory benefit from RoActemra/Actemra therapy within WA19977
  • Treatment with any investigational agent since the last administration of study drug in the core study WA19977 or current participation in another clinical trial except WA19977
  • Patient developed any other autoimmune rheumatic disease or overlap syndrome other than the permitted polyarticular-course JIA subsets: rheumatoid factor positive or negative JIA or extended oligoarticular JIA
  • Patient is pregnant , lactating, or intending to become pregnant during the study and up to 12 weeks after the last administration of study drug
  • Any significant concomitant disease or medical or surgical condition
  • History of significant allergic or infusion reactions to prior biologic therapy
  • Known current active acute, subacute, chronic or history of recurrent infection; patients suffering from ongoing active infections with Epstein Barr virus, herpes zoster or recurrent history of urinary tract infection can be included after the (acute) infection has been excluded or subsided
  • Positive for latent tuberculosis (TB)
  • Currently active asthma for which the patient has required the use of oral or parenteral corticosteroids for >/= 2 weeks within 6 months prior to entering the study
  • Inadequate hepatic, renal or bone marrow function
  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: NCT01667471

Locations
Germany
Bremen, Germany, 28177
Frankfurt/Main, Germany, 60316
Sankt Augustin, Germany, 53757
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: NCT01667471     History of Changes
Other Study ID Numbers: ML25756  2011-001097-25 
Study First Received: August 15, 2012
Results First Received: July 9, 2015
Last Updated: February 1, 2016
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on February 08, 2016