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Efficacy, Safety, Pharmacokinetics and Immunogenicity Study of Abatacept Administered Intravenously to Treat Active Polyarticular-course Juvenile Idiopathic Arthritis in Japan

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01835470
First received: April 17, 2013
Last updated: November 15, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to assess the efficacy of Abatacept after intravenous administration in Japanese children and adolescents with active juvenile idiopathic arthritis who have a history of an inadequate response or intolerance to Methotrexate or biologics

Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: Abatacept
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Open-Label Study to Assess Efficacy, Safety, Pharmacokinetics and Immunogenicity of Abatacept Administered Intravenously in Japanese Children and Adolescents With Active Juvenile Idiopathic Arthritis Who Have a History of an Inadequate Response or Intolerance to Methotrexate or Biologics

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants Experiencing a American College of Rheumatology (ACR) Pediatric 30 Response at Week 16 [ Time Frame: Week 16 (Day 113) ]
    American College of Rheumatology (ACR) pediatric (PED) 30 response was defined as '≥30% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. JIA core set variables defined as the number of active joints, number of joints with Limit of Motion (LOM), physician's global assessment of disease severity, patient global assessment of overall well being, parent assessment of physical function, and acute phase reactant value. A non-responder imputation was applied.


Secondary Outcome Measures:
  • Percentage of Participants Experiencing a American College of Rheumatology Pediatric 50, 70, 90 Response or Inactive Disease at Week 16 [ Time Frame: Week 16 (Day 113) ]
    ACR PED 50 response is defined as '≥50% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 70 response is defined as '≥70% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 90 response is defined as '≥90% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Inactive disease status is defined as no active joints, physician's global assessment of disease severity equal or less than 10mm and C-reactive protein (CRP) within normal limits (0.3 mg/dL). A non-responder imputation is applied. mm=millimeter; mg/dL=milligrams/deciliter

  • Median Percentage of Improvement From Baseline in Physical Function as Assessed by the Childhood Health Assessment Questionnaire (CHAQ) Disability Index at Week 16 [ Time Frame: Week 16 (Day 113) ]
    Physical function was evaluated using the disability section of the Childhood Health Assessment Questionnaire (CHAQ). The questionnaire was derived from the adult HAQ. The disability section assessed physical functions in 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities. The questions were evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 =unable to do. Higher scores indicate greater dysfunction. A disability index was calculated as the mean of the 8 functional scales. The percentage of Improvement from baseline was calculated using the following equation: (Baseline value - Post-baseline value) / Baseline value x 100.

  • Number of Participants With Death, Serious Adverse Events (SAEs), Drug-Related SAEs, Discontinuation Due to Drug-Related SAEs, Drug-Related Adverse Events (AEs), and Discontinuation Due to Drug-Related AEs During the Short Term Period [ Time Frame: Day 1 up to 56 days post Week 16 (Day 113); approximately 6 months ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. SAEs also include hospitalizations for elective surgical procedures. Drug-related=related or missing relationship to study drug. Data includes all events from the date of the first dose of the study drug up to 56 days post the last dose of the study drug in the short-term period or start of the long-term period, whichever occurred first.

  • Maximum Observed Concentration (Cmax) of Abatacept During the Short Term Period [ Time Frame: 9 time points up to Week 16 (Day 113) ]
    Cmax was obtained from the serum concentration versus time data after intravenous administration of abatacept. Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

  • Trough Observed Concentration (Ctrough) of Abatacept During the Short Term Period [ Time Frame: 9 time points up to Week 16 (Day 113) ]
    Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

  • Number of Participants With Positive Immunogenicity During the Short Term Period [ Time Frame: Day 1 up to Week 16 (Day 113) ]
    A positive immunogenicity response for 'Cytotoxic T-lymphocyte antigen (CTLA4), Immunoglobulin (Ig)', 'Ig and/or Junction Region', respectively = (1) missing baseline immunogenicity measurement and positive analytical laboratory reported immunogenicity response post-baseline (2) negative baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline (3) positive baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline with titer value strictly greater than the baseline titer value. Assessment based on assay cutpoint value. Serum samples were collected prior to study medication at Week 0 (Day 1), Week 8 (Day 57), and Week 16 (Day 113) in the short term period. Participants who early discontinued from the study or complete and did not switch to commercial abatacept had a serum sample collected on final visit or early termination visit, 28, 84 and 168 days after the last dose.


Enrollment: 23
Study Start Date: August 2013
Estimated Study Completion Date: December 2018
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abatacept
Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Drug: Abatacept
Other Names:
  • BMS-188667
  • ONO-4164

  Eligibility

Ages Eligible for Study:   4 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have a history of an inadequate therapeutic response or intolerance in the opinion of the examining physician to at least one biologics or Methotrexate (MTX).
  • Diagnosis of Juvenile Idiopathic Arthritis (JIA) by International League of Associations for Rheumatology (ILAR) criteria as oligoarticular, polyarticular Rheumatoid Factor (RF+), polyarticular (RF-), or systemic with a polyarticular-course.
  • Men and women, ages 4 to 17 years, inclusive at enrollment.
  • Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease as defined by:

    1. ≥2 active joints (e.g. presence of swelling, or if no swelling is present, limitation of motion (LOM) accompanied by pain, tenderness, or both) at screening and at Week 0 (Day 1).
    2. ≥2 joints with LOM at screening and at Week 0 (Day 1).

Exclusion Criteria:

  • Systemic onset JIA with any of the following manifestations within the last 6 months prior to enrollment: intermittent fever due to JIA, rheumatoid rash, hepatosplenomegaly, pleuritis, pericarditis, or macrophage activation syndrome.
  • Presence of any other rheumatic disease or major chronic infectious/inflammatory/immunologic disease (e.g. inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, hypogammaglobulinemia, or systemic lupus erythematosus, etc.)
  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: NCT01835470

Locations
Japan
Local Institution
Oobu-shi, Aichi, Japan, 4748710
Local Institution
Sapporo-shi, Hokkaido, Japan, 0048618
Local Institution
Sapporo-shi, Hokkaido, Japan, 0608648
Local Institution
Kobe, Hyogo, Japan, 6500047
Local Institution
Kagoshima-shi, Kagoshima, Japan, 8908520
Local Institution
Yokohama-shi, Kanagawa, Japan, 2328555
Local Institution
Yokohama-shi, Kanagawa, Japan, 2360004
Local Institution
Sendai-shi, Miyagi, Japan, 9893126
Local Institution
Niigata-shi, Niigata, Japan, 9518520
Local Institution
Nakagami-gun, Okinawa, Japan, 9030215
Local Institution
Takatsuki-shi, Osaka, Japan, 5698686
Local Institution
Bunkyo-ku, Tokyo, Japan, 1138603
Local Institution
Shinjuku-ku, Tokyo, Japan, 1620054
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01835470     History of Changes
Other Study ID Numbers: IM101-365
Study First Received: April 17, 2013
Results First Received: November 15, 2016
Last Updated: November 15, 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 22, 2017