Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01575769
First received: April 10, 2012
Last updated: December 3, 2015
Last verified: December 2015
  Purpose
This long-term, interventional, open-label extension study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients from Poland and Russia with polyarticular-course juvenile idiopathic arthritis who completed the WA19977 study. Patients will receive RoActemra/Actemra 8 mg/kg every 4 weeks. The anticipated time on study treatment is 104 weeks.

Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: RoActemra/Actemra (tocilizumab)
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 From Poland and Russia Who Completed the Global, Multinational Trial (WA19977).

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline to 12 weeks after last actual study medication (up to 101 weeks) ] [ Designated as safety issue: No ]
    AE: unfavorable and unintended sign, symptom, or disease associated with use of treatment, regardless of treatment relation. Pre-existing conditions that worsened and laboratory or clinical tests that resulted in change in treatment or discontinuation from treatment were reported as AEs. Serious AE: resulted in death, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically significant. Severe AE: AE that caused inability to work or perform normal daily activity. AEs of special interest: Serious infections (including opportunistic infections), Myocardial infarction/Acute coronary syndrome, Gastrointestinal perforations and related AE, Malignant neoplasms, Anaphylaxis event, Demyelination-related events, Stroke, Spontaneous or serious bleeding, Serious/medically significant hepatic events. Any AE included serious and non-serious AE.


Secondary Outcome Measures:
  • Percentage of Participants With JIA ACR 30 Response at Weeks 12, 24 and End of Follow Up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    JIA ACR30 response was defined as 3 of any 6 core outcome variables improved by at least 30% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: Physician global assessment (PGA) of disease activity using Visual Analog Scale (VAS) from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); Patient/parent global assessment (PtGA) of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and Erythrocyte Sedimentation Rate (ESR).

  • Percentage of Participants With JIA ACR 50 Response at Weeks 12, 24 and End of Follow up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    JIA ACR50 response was defined as 3 of any 6 core outcome variables improved by at least 50% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR.

  • Percentage of Participants With JIA ACR 70 Response at Weeks 12, 24 and End of Follow up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    JIA ACR70 response was defined as 3 of any 6 core outcome variables improved by at least 70% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR

  • Percentage of Participants With JIA ACR 90 Response at Weeks 12, 24 and End of Follow up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    JIA ACR90 response was defined as 3 of any 6 core outcome variables improved by at least 90% of the baseline assessments, with no more than 1 of the remaining variables worsened by more than 30%. Six core variables were: PGA of disease activity using VAS from left end of line 0 (inactive arthritis) to right end of line 100 (very active arthritis); PtGA of overall well-being using a VAS from left end of line 0 (very well) to right end of line 100 (very poor); Number of joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); Number of joints with limitation of movement; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and ESR.

  • Percentage of Participants With Inactive Disease at Week 12, 24 and End of Follow up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]

    Criteria for Inactive Disease:

    1) No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both), 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal ESR (less than [<] 20 millimeters per hour [mm/hour]), and 4) PGA of disease activity using VAS indicated no disease activity (where no disease activity is considered to be a score less than or equal to [≤]10 mm on a 100 mm VAS where left end of line 0 [inactive arthritis] to right end of line 100 [very active arthritis]).


  • Percentage of Participants With Clinical Remission at Week 12, 24 and End of Follow up [ Time Frame: Baseline, Week 12, 24, End of Follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    Clinical remission: inactive disease for minimum of 6 continuous months while on medication (Level 1); off oral corticosteroid medications but still on tocilizumab (Level 2); off both methotrexate and oral corticosteroids but still on tocilizumab (Level 3); or off all anti-arthritis medications-oral corticosteroids, methotrexate, non-steroidal anti-inflammatory drugs but still on tocilizumab (Level 4). Inactive disease: No joints with active arthritis (joints with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both); No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to sJIA; Normal ESR (<20 mm/hour); PGA of disease activity indicated no disease activity (score ≤10 mm on a 100 mm VAS where 0 [inactive arthritis] and 100 [very active arthritis]). Overall percentage of participants with clinical remission (any level) are reported.

  • Change From Baseline in Joints With Active Arthritis at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    Joint with active arthritis was defined as a joint with swelling not due to deformity or joints with limitation of motion and with pain, tenderness or both.

  • Change From Baseline in Number of Joints With Limitation of Movement at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The maximum number of joints with limitation of movement is 67 and these were defined as those with 'limitation of motion'.

  • Change From Baseline in PGA of Disease Activity at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The physician provides a rating of the participant'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 in PtGA of Overall Well-Being at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The participant or parent/guardian, as appropriate, provides a rating of the participant'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 in ESR at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
  • Change From Baseline in Childhood Health Assessment - Disability Index (CHAQ-DI) at Weeks 12, 24, 36, 48, 60, 72, 84, End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, 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. To calculate the overall score, the participant 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.

  • Percentage of Participants With Minimally Important Improvement in the CHAQ-DI Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, 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. To calculate the overall score, the participant 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 minimally important improvement was defined as at least a 0.13 improvement in CHAQ-DI score from baseline.

  • Change From Baseline in CHAQ-DI (Activitiy) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Activity component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Arising) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Arising component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Dressing and Grooming) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Dressing and Grooming component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Eating) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Eating component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Grip) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Grip component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Hygiene) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Hygiene component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Reach) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Reach component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Change From Baseline in CHAQ-DI (Walking) Score at Weeks 12, 24, 36, 48, 60, 72, 84 and End of Follow up [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]
    The CHAQ-DI, as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Walking component was measured on 0-3 scale (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do).

  • Absolute C-Reactive Protein Levels [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, End of follow up (up to 101 weeks) ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: March 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: RoActemra/Actemra (tocilizumab)
Tocilizumab 8 mg/kg every 4 weeks for 104 weeks

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who completed 104 weeks of study WA19977 with at least a JIA ACR30 clinical response to RoActemra/Actemra and no serious adverse event or adverse event
  • Written informed consent obtained from patient if patient is 18 years of age and older, or if under the age of 18 years from parents or legal guardian

Exclusion Criteria:

  • Patient did not benefit from RoActemra/Actemra therapy in study WA19977
  • Treatment with any investigational drug since the last administration of study drug in the core study WA19977
  • Patients developed any other autoimmune rheumatic disease other than the permitted JIA subsets
  • Any significant medical or surgical condition that would jeopardize patient's safety
  • Current serious uncontrolled concomitant disease or infection
  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: NCT01575769

Locations
Poland
Bydgoszcz, Poland, 85-667
Kraków, Poland, 31-503
Lodz, Poland, 91-738
Lublin, Poland, 20-093
Sosnowiec, Poland, 41-218
Russian Federation
Moscow, Russian Federation, 115522
Moscow, Russian Federation, 119021
Moscow, Russian Federation, 119991
Rostov-na-donu, Russian Federation, 344022
Saint-Petersburg, Russian Federation, 194100
Samara, Russian Federation, 443070
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01575769     History of Changes
Other Study ID Numbers: ML27783 
Study First Received: April 10, 2012
Results First Received: August 17, 2015
Last Updated: December 3, 2015
Health Authority: Poland: Ministry of Health

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

ClinicalTrials.gov processed this record on September 29, 2016