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Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously (SC) in Children and Adolescents With Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Inadequate Response (IR) to Biologic or Non Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs)

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ClinicalTrials.gov Identifier: NCT01844518
Recruitment Status : Active, not recruiting
First Posted : May 1, 2013
Results First Posted : March 24, 2016
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to estimate Abatacept steady-state trough concentration (Cmin) at Day 113 in children and adolescents with pJIA

Condition or disease Intervention/treatment Phase
Active Polyarticular Juvenile Idiopathic Arthritis Biological: Abatacept Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 187 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Multi-center, Open-Label Study to Evaluate Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously (SC) in Children and Adolescents With Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Inadequate Response (IR) to Biologic or Non Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs)
Actual Study Start Date : June 28, 2013
Actual Primary Completion Date : March 12, 2015
Estimated Study Completion Date : December 29, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Abatacept

Arm Intervention/treatment
Experimental: Short and Long Terms: Orencia

Short Term: Orencia 50 mg/mL, 87.5 mg/mL, 125 mg/mL pre-filled syringes subcutaneously (0.4 mL/0.7 mL/1.0 mL) weekly for 4 months

Long term: Orencia 50 mg/mL, 87.5 mg/mL, 125 mg/mL pre-filled syringes subcutaneously (0.4 mL/0.7 mL/1.0 mL) weekly for 20 months

Biological: Abatacept
Other Name: Orencia




Primary Outcome Measures :
  1. Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 [ Time Frame: Day 113 ]
    Trough concentration of abatacept (reported as geometric mean of Cmin) in all pharmacokinetic (PK)-evaluable participants. Cmin is reported in microgram per milliliter (µg/mL). Desired target therapeutic Cmin should be >= 10 µg/mL.


Secondary Outcome Measures :
  1. Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30) [ Time Frame: Day 113 ]
    ACRp30 is defined as ≥30% improvement in at least 3 of the 6 juvenile idiopathic arthritis (JIA) core set variables [number of active joints, number of joints with limitation of motion (LOM), physician global assessment of disease activity, parent global assessment of patient overall well-being, functional ability as measured by the Children's Health Assessment Questionnaire (CHAQ) and C-reactive protein (CRP)] and ≥30% worsening in not more than 1 of the remaining 6 JIA core set variables.

  2. Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 [ Time Frame: Days 57, 85 and 113 ]
    Evaluation of the trough concentration of abatacept (reported as geometric mean of Cmin) in all pk-evaluable participants at Days 57, 85 and 113 during a 4-month treatment period. Weight-tiered dosing groups are based on the first dose the participant received. Cmin is reported in microgram per milliliter (µg/mL).

  3. Number of Participants (Ages 6 to 17) With Adverse Events (AEs), Deaths, Serious AEs (SAEs) and AEs Leading to Discontinuation in the Short Term Period [ Time Frame: Day 1 up to 56 days after last dose up to March 2015 ]

    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. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.


  4. Number of Participants (Ages 6 to 17) With Adverse Events (AEs) of Special Interest in the Short Term Period [ Time Frame: Day 1 up to 56 days after last dose up to March 2015 ]

    AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.

    AEs of special interest include infections, autoimmune disorders, malignancies, local injection site reactions and AEs within 24 hours of study drug administration.

    The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.


  5. Number of Participants (Ages 6 to 17) With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period [ Time Frame: Day 1 up to 56 days after last dose up to March 2015 ]

    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. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.


  6. Number of Participants (Ages 6 to 17) With Adverse Events (AEs) of Special Interest in the Cumulative Period [ Time Frame: Day 1 up to 56 days after last dose, up to March 2015 ]

    AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.

    AEs of special interest include infections, autoimmune disorders, malignancies, local injection site reactions and AEs within 24 hours of study drug administration.

    The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.


  7. Number of Participants (Ages 6 to 17) With Positive Immunogenicity Response in the Short Term Period [ Time Frame: Day 1 to 168 days after the last dose of study medication in the short-term period ]
    Overall number of participants with either a positive immunogenicity response for 'CTLA4 and possibly Ig' or 'Ig and/or Junction Region' relative to baseline. Sample draws for immunogenicity were scheduled at specific study days while on treatment for all subjects and at follow-up visits 28, 85, and 168 days after the last abatacept dose for those subjects who discontinued from the ST period or completed the ST study without continuing abatacept treatment.

  8. Number of Participants (Ages 6 to 17) With Positive Immunogenicity Response in the Cumulative Period [ Time Frame: Day 1 to 6 months following discontinuation of treatment, up to March 2015 ]
    Overall number of participants with either a positive immunogenicity response for 'CTLA4 and possibly Ig' or 'Ig and/or Junction Region' relative to baseline. Sample draws for immunogenicity were scheduled at specific study days while on treatment for all subjects and at follow-up visits 28, 85, and 168 days after the last abatacept dose regardless of whether they discontinued early in the ST or LTE period, elected not to enter the LTE period, or completed both ST and LTE periods.



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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • JIA subjects (male or female), ages 2-17 years with active disease who had an insufficient therapeutic response or intolerance to at least one non biologic DMARD or Tumor Necrosis Factor (TNFα) antagonists for at least 3 months prior to screening
  • Subjects with TNFα inadequate response (or prior biologic) will be restricted to 30% of the population
  • Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease with ≥2 active joints and ≥2 joints with limitation of motion.

Exclusion Criteria:

  • Subjects with other rheumatic diseases or major chronic inflammatory/immunologic diseases, active uveitis, systemic JIA with active systemic features (within a period of 6 months prior to enrollment), persistent Oligoarthritis JIA, or failed 3 or more TNFα antagonists or other biological DMARDs will be excluded.
  • Active systemic disease: (ie, extra-articular features of systemic JIA including fever, rash, organomegaly) within a period of 6 months prior to randomization.
  • Subjects who have failed more than two TNFα antagonists or other biologic DMARDs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01844518


  Show 55 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01844518     History of Changes
Other Study ID Numbers: IM101-301
2012-003195-39 ( EudraCT Number )
First Posted: May 1, 2013    Key Record Dates
Results First Posted: March 24, 2016
Last Update Posted: February 15, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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