Back to resultsA Long-Term Extension Study of RoActemra/Actemra (Tocilizumab) in Patients With Juvenile Idiopathic Arthritis From France Who Completed WA19977 Core Study
Primary Purpose
Juvenile Idiopathic Arthritis
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
tocilizumab [RoActemra/Actemra]
Sponsored by
About this trial
This is an interventional treatment trial for Juvenile Idiopathic Arthritis
Eligibility Criteria
Inclusion Criteria:
- Patients who completed visit 33 (week 104) of WA19977 study and who may benefit from study drug treatment according to the investigator's assessment
- Patients have to receive the first RoActemra/Actemra infusion in this study at the Week 8 visit at the latest
- 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
- Patient developed any other autoimmune rheumatic disease or overlap syndrome other than the permitted polyarticular-course Juvenile Idiopathic Arthritis (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
- Currently active primary or secondary immunodeficiency
- Any infections with contraindications to RoActemra/Actemra therapy according to investigator judgment
- Inadequate hepatic, renal or bone marrow function
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RoActemra/Actemra
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Any Adverse Events and Any Serious Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Number of Participants With Adverse Events of Special Interest
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. The AEs of special interests included gingival bleeding, tooth abscess, acarodermatitis, ear infection, gastroenteritis, herpes zoster ophthalmic, lice infestation, nasopharyngitis, oral fungal infection, oral herpes, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheitis, tracheobronchitis, urinary tract infection, menorrhagia, asthma, epistaxis, and hematoma.
Number of Participants With Adverse Events Related to Tocilizumab
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. Relatedness of any AEs was reported as possibly related, probably related, or remotely related to TCZ.
Secondary Outcome Measures
Mean Exposure to Study Treatment
Participants received TCZ for Week 104 or when TCZ was commercially available for pcJIA participants, whichever comes first in France. The mean TCZ exposure (time from first to last administration) was reported.
Mean Duration of Study Follow-Up
The participants were followed-up from Day 1 to last visit date (approximately 2 years). Mean time for which participants were followed up in the study was reported.
Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths
Number of participants with AEs leading to TCZ modification, AEs leading to death, anaphylaxis or serious hypersensitivity, and deaths were reported.
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Clinically significant abnormal parameters included eosinophil count, alanine aminotransferase, total bilirubin, and protein and blood in urine. Number of participants with these abnormal lab parameters was reported.
Number of Participants With Abnormality in Physical Examinations
Participants with abnormal physical examinations of ear, nose and throat (asthma); extremities (synovitis, sequelae with flexion of the 5th right proximal interphalangeal joint, hallux valgus, deviations of metatarsophalangeal joints, and callus under metatarsal head); lung (mild bronchospasm); skin (vitiligo and hematoma, fatty subcutaneous infiltration on the neck, cutaneous eruption, and scalp pediculosis); and musculoskeletal system (discomfort in right hip) were reported.
Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70
The Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) is comprised of six components: Maximum number of joints with active arthritis; Number of joints with limitation of movement; Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP); Childhood Health Assessment Questionnaire-Disease Index (CHAQ-DI) graded on 4-point scales [0 = without any difficulty and 3 = unable to do] of 30 items grouped into 8 domains of physical function; Physician's global assessment of disease activity and Participant's global assessment of overall well-being (both assessed on a 0 to 100 mm Visual Analogue Scale [VAS], where score 0 = inactive arthritis and 100 = very active arthritis). A JIA ACR50/70 response is defined as improvement in at least three of the six core components by at least 50 percent (%), or 70%, respectively and no more than one of the remaining core components worsening by more than 30%.
Number of Participants With Inactive Disease
Inactive disease was defined as: 1) No joints with active arthritis (no swollen, painful and lack of motion joints), 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) No disease activity according to Physician's global assessment of disease activity (<= 10 millimeters [mm] on a VAS). The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active'.
Number of Participants Achieving Clinical Remission
Clinical remission was defined as inactive disease observed for at least 6 continuous months. Clinical remission was defined as per medication uptake as: Level 1 (clinical remission on medication), Level 2 (clinical remission off oral corticosteroid medication [still on TCZ]), Level 3 (clinical remission off both oral corticosteroid and methotrexate medication [still on TCZ]), and Level 4 (clinical remission off all anti-inflammatory medications [still on TCZ]). Number of participants at each clinical remission level was reported.
Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index
The CHAQ-DI included questions on dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The disability index (DI) of the original CHAQ was graded on 4-point categorical scales of 30 items grouped into 8 domains of physical function. The highest scoring item in each domain determined the score for that domain. The score for the disability index was the mean of domain scores ranging from 0 to 3 (0 = without any difficulty and 3 = unable to do) with higher scores meaning higher disability. Minimally important improvement in CHAQ-DI was defined as a change from baseline of WA19977 core study (Day 1/Visit 1) >=0.13 at each visit.
Number of Joints With Limitation of Motion
The most frequent symptom reported by most participants was a limitation of motion (LOM) of joints and it was determined by physical examination. The mean joints with limitation of motion were reported.
Number of Joints With Active Range of Motion
The active range of motion joints was counted by physical examination and mean joints was reported.
Number of Swollen Joints
The swollen joints was counted by physical examination and mean swollen joints were reported.
Number of Painful Joints
The painful joints were counted by physical examination and mean painful joints was reported.
Physician's Global Assessment of Disease Activity
The Physician's global assessment of disease activity was recorded on a 0 to 100 mm horizontal VAS where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active' (higher score indicate worsening of disease).
Parent/Patient's Global Assessment of Disease Activity
Parent/patient global assessment of disease activity was performed using 0 to 100 mm VAS, and higher the score of VAS, worse the disease status (0= absence of activity or sign or symptom; 100= maximal activity or signs or symptoms). No disease activity was defined as VAS <=10 mm.
Parent/Patient's Discomfort Index (Pain)
Participants or parents rated participant's pain by placing a horizontal line on a VAS of 0 (no pain) - 100 mm (unbearable pain). To describe the pain, a cut-off at 10 mm was used, and VAS <10 mm was defined as no pain.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01673919
Brief Title
A Long-Term Extension Study of RoActemra/Actemra (Tocilizumab) in Patients With Juvenile Idiopathic Arthritis From France Who Completed WA19977 Core Study
Official Title
Long-term, Interventional, Open Label Extension Study Evaluating the Safety of Tocilizumab Treatment in Patients With Polyarticular-course Juvenile Idiopathic Arthritis From France Who Completed the Global, Multinational Trial (WA19977)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
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 will continue to receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks. Anticipated time on study treatment is 104 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RoActemra/Actemra
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg iv every 4 weeks, 104 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Any Adverse Events and Any Serious Adverse Events
Description
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Time Frame
Approximately 2 years
Title
Number of Participants With Adverse Events of Special Interest
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. The AEs of special interests included gingival bleeding, tooth abscess, acarodermatitis, ear infection, gastroenteritis, herpes zoster ophthalmic, lice infestation, nasopharyngitis, oral fungal infection, oral herpes, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheitis, tracheobronchitis, urinary tract infection, menorrhagia, asthma, epistaxis, and hematoma.
Time Frame
Approximately 2 years
Title
Number of Participants With Adverse Events Related to Tocilizumab
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. Relatedness of any AEs was reported as possibly related, probably related, or remotely related to TCZ.
Time Frame
Approximately 2 years
Secondary Outcome Measure Information:
Title
Mean Exposure to Study Treatment
Description
Participants received TCZ for Week 104 or when TCZ was commercially available for pcJIA participants, whichever comes first in France. The mean TCZ exposure (time from first to last administration) was reported.
Time Frame
Approximately 2 years
Title
Mean Duration of Study Follow-Up
Description
The participants were followed-up from Day 1 to last visit date (approximately 2 years). Mean time for which participants were followed up in the study was reported.
Time Frame
Approximately 2 years
Title
Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and Deaths
Description
Number of participants with AEs leading to TCZ modification, AEs leading to death, anaphylaxis or serious hypersensitivity, and deaths were reported.
Time Frame
Approximately 2 years
Title
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Description
Clinically significant abnormal parameters included eosinophil count, alanine aminotransferase, total bilirubin, and protein and blood in urine. Number of participants with these abnormal lab parameters was reported.
Time Frame
Approximately 2 years
Title
Number of Participants With Abnormality in Physical Examinations
Description
Participants with abnormal physical examinations of ear, nose and throat (asthma); extremities (synovitis, sequelae with flexion of the 5th right proximal interphalangeal joint, hallux valgus, deviations of metatarsophalangeal joints, and callus under metatarsal head); lung (mild bronchospasm); skin (vitiligo and hematoma, fatty subcutaneous infiltration on the neck, cutaneous eruption, and scalp pediculosis); and musculoskeletal system (discomfort in right hip) were reported.
Time Frame
Approximately 2 years
Title
Number of Participants With Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70
Description
The Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) is comprised of six components: Maximum number of joints with active arthritis; Number of joints with limitation of movement; Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP); Childhood Health Assessment Questionnaire-Disease Index (CHAQ-DI) graded on 4-point scales [0 = without any difficulty and 3 = unable to do] of 30 items grouped into 8 domains of physical function; Physician's global assessment of disease activity and Participant's global assessment of overall well-being (both assessed on a 0 to 100 mm Visual Analogue Scale [VAS], where score 0 = inactive arthritis and 100 = very active arthritis). A JIA ACR50/70 response is defined as improvement in at least three of the six core components by at least 50 percent (%), or 70%, respectively and no more than one of the remaining core components worsening by more than 30%.
Time Frame
Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Number of Participants With Inactive Disease
Description
Inactive disease was defined as: 1) No joints with active arthritis (no swollen, painful and lack of motion joints), 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) No disease activity according to Physician's global assessment of disease activity (<= 10 millimeters [mm] on a VAS). The participant's treating physician provided a rating of the participant's arthritis disease activity on a 0 to 100 mm horizontal scale where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active'.
Time Frame
Weeks 24, 36, 48, 72, and 108
Title
Number of Participants Achieving Clinical Remission
Description
Clinical remission was defined as inactive disease observed for at least 6 continuous months. Clinical remission was defined as per medication uptake as: Level 1 (clinical remission on medication), Level 2 (clinical remission off oral corticosteroid medication [still on TCZ]), Level 3 (clinical remission off both oral corticosteroid and methotrexate medication [still on TCZ]), and Level 4 (clinical remission off all anti-inflammatory medications [still on TCZ]). Number of participants at each clinical remission level was reported.
Time Frame
Weeks 24, 36, 48, 72, and 108
Title
Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability Index
Description
The CHAQ-DI included questions on dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The disability index (DI) of the original CHAQ was graded on 4-point categorical scales of 30 items grouped into 8 domains of physical function. The highest scoring item in each domain determined the score for that domain. The score for the disability index was the mean of domain scores ranging from 0 to 3 (0 = without any difficulty and 3 = unable to do) with higher scores meaning higher disability. Minimally important improvement in CHAQ-DI was defined as a change from baseline of WA19977 core study (Day 1/Visit 1) >=0.13 at each visit.
Time Frame
Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Number of Joints With Limitation of Motion
Description
The most frequent symptom reported by most participants was a limitation of motion (LOM) of joints and it was determined by physical examination. The mean joints with limitation of motion were reported.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Number of Joints With Active Range of Motion
Description
The active range of motion joints was counted by physical examination and mean joints was reported.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Number of Swollen Joints
Description
The swollen joints was counted by physical examination and mean swollen joints were reported.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Number of Painful Joints
Description
The painful joints were counted by physical examination and mean painful joints was reported.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Physician's Global Assessment of Disease Activity
Description
The Physician's global assessment of disease activity was recorded on a 0 to 100 mm horizontal VAS where score 0 represented 'arthritis inactive' (i.e., symptom-free and no arthritis symptoms) and score 100 represented 'arthritis very active' (higher score indicate worsening of disease).
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Parent/Patient's Global Assessment of Disease Activity
Description
Parent/patient global assessment of disease activity was performed using 0 to 100 mm VAS, and higher the score of VAS, worse the disease status (0= absence of activity or sign or symptom; 100= maximal activity or signs or symptoms). No disease activity was defined as VAS <=10 mm.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
Title
Parent/Patient's Discomfort Index (Pain)
Description
Participants or parents rated participant's pain by placing a horizontal line on a VAS of 0 (no pain) - 100 mm (unbearable pain). To describe the pain, a cut-off at 10 mm was used, and VAS <10 mm was defined as no pain.
Time Frame
Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who completed visit 33 (week 104) of WA19977 study and who may benefit from study drug treatment according to the investigator's assessment
Patients have to receive the first RoActemra/Actemra infusion in this study at the Week 8 visit at the latest
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
Patient developed any other autoimmune rheumatic disease or overlap syndrome other than the permitted polyarticular-course Juvenile Idiopathic Arthritis (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
Currently active primary or secondary immunodeficiency
Any infections with contraindications to RoActemra/Actemra therapy according to investigator judgment
Inadequate hepatic, renal or bone marrow function
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Le Kremlin Bicêtre
ZIP/Postal Code
94275
Country
France
City
Montpellier
ZIP/Postal Code
34295
Country
France
City
Paris
ZIP/Postal Code
75679
Country
France
City
Paris
ZIP/Postal Code
75743
Country
France
12. IPD Sharing Statement
Learn more about this trial
A Long-Term Extension Study of RoActemra/Actemra (Tocilizumab) in Patients With Juvenile Idiopathic Arthritis From France Who Completed WA19977 Core Study
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