Active Polyarticular Juvenile Idiopathic Arthritis
Conditions
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
Interventions
BIOLOGICALAbatacept
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
Countries
Argentina, Belgium, Brazil, France, Germany, Italy, Mexico, Peru, Russia, South Africa, Spain, United States
Participant flow
Pre-assignment details
219 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| SC Abatacept Ages 6 to 17 Subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to the following weight-tiered dosing regimen: 10 to less than (\<) 25 kilogram (kg) (50 milligram \[mg\] in 0.4 milliliter \[mL\] PFS), 25 to \< 50 kg (87.5 mg in 0.7 mL PFS) and 50 kg (125 mg in 1 mL PFS). | 173 |
| SC Abatacept Ages 2 to 5 SC abatacept administered by PFS once weekly according to the following weight-tiered dosing regimen: 10 to \< 25 kg (50 mg in 0.4 mL PFS), 25 to \< 50 kg (87.5 mg in 0.7 mL PFS) and 50 kg (125 mg in 1 mL PFS). | 46 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 1 |
| Overall Study | Lack of Efficacy | 17 | 5 |
| Overall Study | No Longer Met Study Criteria | 2 | 0 |
| Overall Study | Participant's request to discontinue | 4 | 1 |
| Overall Study | Poor/Non-compliance | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 0 |
Baseline characteristics
| Characteristic | SC Abatacept Ages 6 to 17 | SC Abatacept Ages 2 to 5 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 173 Participants | 46 Participants | 219 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 14 Participants | 1 Participants | 15 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 15 Participants | 1 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 144 Participants | 44 Participants | 188 Participants |
| Sex: Female, Male Female | 136 Participants | 28 Participants | 164 Participants |
| Sex: Female, Male Male | 37 Participants | 18 Participants | 55 Participants |
| Weight <25 kg | 18 Participants | 43 Participants | 61 Participants |
| Weight 25 to 50 kg | 74 Participants | 3 Participants | 77 Participants |
| Weight >=50 kg | 81 Participants | 0 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 173 | 0 / 46 |
| other Total, other adverse events | 127 / 173 | 44 / 46 |
| serious Total, serious adverse events | 18 / 173 | 6 / 46 |
Outcome results
Primary
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.
Time frame: Day 113
Population: All treated participants with available PK measurements. Endpoint pre-specified to only be collected for 6-17 year age group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SC Abatacept Ages 6 to 17 | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 | 39.7 µg/mL | Geometric Coefficient of Variation 35 |
Secondary
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.
Time frame: Days 57, 85 and 113
Population: All treated participants with available PK measurements in the 6-17 Year Age-Group Cohort. Endpoint pre-specified to only be collected for 6-17 year age group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SC Abatacept Ages 6 to 17 | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 85 | 27.7 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 38 |
| SC Abatacept Ages 6 to 17 | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 57 | 29.5 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 32 |
| SC Abatacept Ages 6 to 17 | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 113 | 34.3 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 39 |
| 25 to <50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 113 | 44.2 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 34 |
| 25 to <50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 57 | 36.2 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 35 |
| 25 to <50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 85 | 42.5 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 32 |
| >=50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 85 | 36.0 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 40 |
| >=50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 113 | 36.6 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 31 |
| >=50 kg Dosing Group | Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose | Day 57 | 33.0 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 33 |
Secondary
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.
Time frame: From first dose up to 56 days after last dose ( up to approximately 2 years)
Population: All treated participants in the cumulative period
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Drug-Related SAEs | 1 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Overall AEs | 152 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | SAEs | 14 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Treatment-Related AEs | 54 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Discontinuation Due to SAEs | 4 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Discontinuation Due to AEs | 7 Participants |
| SC Abatacept Ages 6 to 17 | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Deaths | 0 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Discontinuation Due to AEs | 1 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Deaths | 0 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | SAEs | 5 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Drug-Related SAEs | 2 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Discontinuation Due to SAEs | 0 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Overall AEs | 44 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period | Treatment-Related AEs | 30 Participants |
Secondary
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.
Time frame: From first dose up to 56 days post last dose in the short-term period (initial 4-month treatment period)
Population: All treated participants in the short-term period in the 6-17 Year Age Group Cohort. Endpoint pre-specified to only be collected for 6-17 year age group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SC Abatacept Ages 6 to 17 | 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 | Deaths | 0 Participants |
| SC Abatacept Ages 6 to 17 | 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 | SAEs | 5 Participants |
| SC Abatacept Ages 6 to 17 | 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 | Drug-Related SAEs | 1 Participants |
| SC Abatacept Ages 6 to 17 | 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 | Discontinuation due to SAEs | 2 Participants |
| SC Abatacept Ages 6 to 17 | 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 | Overall AEs | 102 Participants |
| SC Abatacept Ages 6 to 17 | 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 | Drug-Related AEs | 36 Participants |
| SC Abatacept Ages 6 to 17 | 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 | Discontinuation due to AEs | 3 Participants |
Secondary
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.
Time frame: From first dose up to 6 months following treatment discontinuation (up to approximately 2 years)
Population: All treated participants in the cumulative period with available immunogenicity measurements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC Abatacept Ages 6 to 17 | Number of Participants With Positive Immunogenicity Response in the Cumulative Period | 8 Participants |
| 25 to <50 kg Dosing Group | Number of Participants With Positive Immunogenicity Response in the Cumulative Period | 7 Participants |
Secondary
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.
Time frame: 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)
Population: All treated participants in the short-term period with available immunogenicity measurements in the 6-17 Year Age-Group Cohort. Endpoint pre-specified to only be collected for 6-17 year age group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC Abatacept Ages 6 to 17 | Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort | 3 Participants |
Secondary
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: 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.
Time frame: Day 113
Population: All treated participants in the 6-17 Year Age-Group Cohort. Endpoint prespecified to only be collected for 6-17 year age group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SC Abatacept Ages 6 to 17 | Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30) | 83.2 Percentage of participants |