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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01673919
First received: August 23, 2012
Last updated: September 14, 2016
Last verified: November 2015
  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 will continue 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: 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 France 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 Any Adverse Events and Any Serious Adverse Events [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 24, 36, 48, 72, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 24, 36, 48, 72, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    The active range of motion joints was counted by physical examination and mean joints was reported.

  • Number of Swollen Joints [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    The swollen joints was counted by physical examination and mean swollen joints were reported.

  • Number of Painful Joints [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    The painful joints were counted by physical examination and mean painful joints was reported.

  • Physician's Global Assessment of Disease Activity [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Day 1), Weeks 12, 24, 36, 48, 60, 72, 84, and 108 ] [ Designated as safety issue: No ]
    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.


Enrollment: 7
Study Start Date: February 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (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:   4 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01673919

Locations
France
Le Kremlin Bicêtre, France, 94275
Montpellier, France, 34295
Paris, France, 75679
Paris, France, 75743
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01673919     History of Changes
Other Study ID Numbers: ML28166  2011-005515-90 
Study First Received: August 23, 2012
Results First Received: September 14, 2016
Last Updated: September 14, 2016
Health Authority: France: Agence Nationale de Sécurite du Médicament et des Produits de Santé - ANSM

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 December 02, 2016