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
- Active Polyarticular Juvenile Idiopathic Arthritis
- Interventions
- Biological: Abatacept
- Registration Number
- NCT01844518
- Lead Sponsor
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Short and Long Terms: Orencia Abatacept 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
- Primary Outcome Measures
Name Time Method Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 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
Name Time Method Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period From first dose up to 56 days after last dose ( up to approximately 2 years) 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.
Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort 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) 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.
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 From first dose up to 56 days post last dose in the short-term period (initial 4-month treatment 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.
Number of Participants With Positive Immunogenicity Response in the Cumulative Period From first dose up to 6 months following treatment discontinuation (up to approximately 2 years) 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.
Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose 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. 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.
Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30) Day 113 ACRp30 is defined as ≥30% improvement in at least 3 of the 6 juvenile idiopathic arthritis (JIA) core set variables:
1. number of active joints
2. number of joints with limitation of motion (LOM)
3. physician global assessment of disease activity
4. parent global assessment of patient overall well-being
5. functional ability as measured by the Children's Health Assessment Questionnaire (CHAQ)
6. 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.
Trial Locations
- Locations (55)
Riley Hospital For Children
🇺🇸Indianapolis, Indiana, United States
Seattle Children'S Hospital
🇺🇸Seattle, Washington, United States
Local Institution - 0036
🇧🇪Gent, Belgium
Local Institution - 0049
🇧🇪Leuven, Belgium
Local Institution - 0038
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 0026
🇵🇪Lima, Peru
Local Institution - 0033
🇿🇦Cape Town, Western CAPE, South Africa
Local Institution - 0029
🇦🇷Rosario, Santa FE, Argentina
Local Institution - 0005
🇺🇸Portland, Oregon, United States
Local Institution - 0007
🇺🇸Birmingham, Alabama, United States
Local Institution - 0004
🇺🇸Salt Lake City, Utah, United States
Local Institution - 0003
🇺🇸Little Rock, Arkansas, United States
Local Institution - 0009
🇺🇸Chicago, Illinois, United States
Local Institution - 0002
🇺🇸Bronx, New York, United States
Local Institution - 0001
🇺🇸Kansas City, Missouri, United States
Local Institution - 0030
🇦🇷Buenos Aires, Argentina
Local Institution - 0037
🇧🇪Bruxelles, Belgium
Local Institution - 0064
🇦🇷Caba, Argentina
Local Institution - 0028
🇦🇷San Miguel De Tucuman, Tucuman, Argentina
Local Institution - 0018
🇫🇷Bron Cedex, France
Local Institution - 0042
🇧🇷Sao Paulo, Brazil
Local Institution - 0040
🇧🇷Sao Paulo, Brazil
Local Institution - 0041
🇧🇷Sao Paulo, Brazil
Local Institution - 0014
🇫🇷Paris Cedex 15, France
Local Institution - 0017
🇫🇷Poitiers, France
Local Institution - 0015
🇫🇷Strasbourg Cedex, France
Local Institution - 0016
🇫🇷Le Kremlin Bicetre Cedex, France
Local Institution - 0044
🇩🇪Bad Bramstedt, Germany
Local Institution - 0045
🇩🇪Berlin, Germany
Local Institution - 0048
🇩🇪Heidelberg, Germany
Local Institution - 0047
🇩🇪Sankt Augustin, Germany
Local Institution - 0046
🇩🇪Hamburg, Germany
Local Institution - 0022
🇮🇹Milano, Italy
Local Institution - 0059
🇲🇽Mexico, Distrito Federal, Mexico
Local Institution - 0062
🇮🇹Napoli, Italy
Local Institution - 0057
🇲🇽Mexico City, Distrito Federal, Mexico
Local Institution - 0060
🇲🇽Guadalajara, Jalisco, Mexico
Local Institution - 0056
🇲🇽Monterrey, Nuevo Leon, Mexico
Local Institution - 0058
🇲🇽Merida, Yucatan, Mexico
Local Institution - 0027
🇵🇪Lima, Peru
Local Institution - 0025
🇵🇪Lima, Peru
Local Institution - 0068
🇷🇺Tolyatti, Russian Federation
Local Institution - 0035
🇿🇦Park West, Bloemfontein, FREE State, South Africa
Local Institution - 0034
🇿🇦Pretoria, Gauteng, South Africa
Local Institution - 0032
🇿🇦Pretoria, Gauteng, South Africa
Local Institution - 0053
🇪🇸Madrid, Spain
Local Institution - 0052
🇪🇸Valencia, Spain
Local Institution - 0055
🇪🇸Madrid, Spain
Local Institution - 0031
🇦🇷Cordoba, Argentina
Local Institution
🇵🇪Lima, Peru
Local Institution - 0061
🇮🇹Firenze, Italy
Local Institution - 0050
🇪🇸Barcelona, Spain
Local Institution - 0011
🇺🇸Hartford, Connecticut, United States
Local Institution - 0008
🇺🇸Cincinnati, Ohio, United States
University Of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States