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

Phase 3
Completed
Conditions
Juvenile Idiopathic Arthritis
Interventions
Registration Number
NCT01673919
Lead Sponsor
Hoffmann-La Roche
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
7
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RoActemra/Actemratocilizumab [RoActemra/Actemra]-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Any Adverse Events and Any Serious Adverse EventsApproximately 2 years

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 InterestApproximately 2 years

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 TocilizumabApproximately 2 years

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
NameTimeMethod
Mean Duration of Study Follow-UpApproximately 2 years

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 Juvenile Idiopathic Arthritis American College of Rheumatology Response 50/70Weeks 12, 24, 36, 48, 60, 72, 84, and 108

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 Achieving Clinical RemissionWeeks 24, 36, 48, 72, and 108

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.

Mean Exposure to Study TreatmentApproximately 2 years

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.

Number of Participants With AEs Leading to TCZ Modification, AEs Leading to Death, Anaphylaxis or Serious Hypersensitivity and DeathsApproximately 2 years

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 ParametersApproximately 2 years

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 Joints With Limitation of MotionBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

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 Participants With Inactive DiseaseWeeks 24, 36, 48, 72, and 108

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 Painful JointsBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

The painful joints were counted by physical examination and mean painful joints was reported.

Number of Participants With Abnormality in Physical ExaminationsApproximately 2 years

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 Joints With Active Range of MotionBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

The active range of motion joints was counted by physical examination and mean joints was reported.

Physician's Global Assessment of Disease ActivityBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

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 ActivityBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

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)Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

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.

Number of Participants With a Minimally Important Improvement in the Childhood Health Assessment Questionnaire-Disability IndexWeeks 12, 24, 36, 48, 60, 72, 84, and 108

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 Swollen JointsBaseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108

The swollen joints was counted by physical examination and mean swollen joints were reported.

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