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)

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

Official Title
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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)

Conditions
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Active Polyarticular Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Biological: Abatacept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short and Long Terms: Orencia<br>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<br> <br> * Other names: Orencia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 | 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. | Day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30) | 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) C-reactive protein (CRP). In addition to the above condition, to be considered a responder participants cannot have ≥30% worsening in more than 1 of the 3 remaining JIA core set variables for which improvement was not observed. | Day 113 | 
| Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Evaluation of the trough concentration of abatacept (reported as geometric mean of Cmin) in all pk-evaluable participants at Days 57, 85 and 113. Weight-tiered dosing groups are based on the first dose the participant received. Cmin is reported in microgram per milliliter (µg/mL). Here 'n' number analyzed signifies participants who were evaluable for each time point. | Days 57, 85 and 113 | 
| Number of Participants With Adverse Events (AEs), Deaths, Serious AEs (SAEs) and AEs Leading to Discontinuation in the Short-Term Period for the 6-17 Year Age-Group Cohort | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose which results in death, is life threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. | From first dose up to 56 days post last dose in the short-term period (initial 4-month treatment period) | 
| Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose which results in death, is life threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. | From first dose up to 56 days after last dose ( up to approximately 2 years) | 
| Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort | 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 short term (ST) period (initial 4-month treatment period) or completed the ST study without continuing abatacept treatment. | From first dose up to start of LT (for those continuing in long-term) or up to 168 days after the lost dose of study medication in the ST period (for those not entering in the long-term) | 
| Number of Participants With Positive Immunogenicity Response in the Cumulative 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 regardless of whether they discontinued early in the short term (ST) or long term (LT) period, elected not to enter the LT period, or completed both ST and LT periods. | From first dose up to 6 months following treatment discontinuation (up to approximately 2 years) |