Trial Outcomes & Findings for 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) (NCT NCT01844518)

Last Updated: 2023-07-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

219 participants

Primary outcome timeframe

Day 113

Results posted on

2023-07-12

Participant Flow

219 participants were treated.

Participant milestones

Participant milestones
Measure	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).	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).
Overall Study STARTED	173	46
Overall Study COMPLETED	132	39
Overall Study NOT COMPLETED	41	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).
Overall Study Adverse Event	7	1
Overall Study Lack of Efficacy	17	5
Overall Study Participant's request to discontinue	4	1
Overall Study Poor/Non-compliance	1	0
Overall Study No Longer Met Study Criteria	2	0
Overall Study Withdrawal by Subject	9	0
Overall Study Pregnancy	1	0

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SC Abatacept Ages 6 to 17 n=173 Participants 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).	SC Abatacept Ages 2 to 5 n=46 Participants 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).	Total n=219 Participants Total of all reporting groups
Age, Categorical <=18 years	173 Participants n=5 Participants	46 Participants n=7 Participants	219 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	136 Participants n=5 Participants	28 Participants n=7 Participants	164 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	14 Participants n=5 Participants	1 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	144 Participants n=5 Participants	44 Participants n=7 Participants	188 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	15 Participants n=5 Participants	1 Participants n=7 Participants	16 Participants n=5 Participants
Weight <25 kg	18 Participants n=5 Participants	43 Participants n=7 Participants	61 Participants n=5 Participants
Weight 25 to 50 kg	74 Participants n=5 Participants	3 Participants n=7 Participants	77 Participants n=5 Participants
Weight >=50 kg	81 Participants n=5 Participants	0 Participants n=7 Participants	81 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 113

Population: All treated participants with available PK measurements. Endpoint pre-specified to only be collected for 6-17 year age group.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=131 Participants 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).	25 to <50 kg Dosing Group Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17	39.7 µg/mL Geometric Coefficient of Variation 35	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=173 Participants 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).	25 to <50 kg Dosing Group Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30)	83.2 Percentage of participants Interval 77.7 to 88.8	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=17 Participants 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).	25 to <50 kg Dosing Group n=69 Participants Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group n=74 Participants Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
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	36.2 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 35	33.0 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 33
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	42.5 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 32	36.0 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 40
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	44.2 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 34	36.6 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 31

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=173 Participants 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).	25 to <50 kg Dosing Group Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—

SECONDARY outcome

Timeframe: From first dose up to 56 days after last dose ( up to approximately 2 years)

Population: All treated participants in the cumulative period

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=173 Participants 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).	25 to <50 kg Dosing Group n=46 Participants Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period Overall AEs	152 Participants	44 Participants	—
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period Deaths	0 Participants	0 Participants	—
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period SAEs	14 Participants	5 Participants	—
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period Drug-Related SAEs	1 Participants	2 Participants	—
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	0 Participants	—
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period Treatment-Related AEs	54 Participants	30 Participants	—
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	1 Participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=171 Participants 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).	25 to <50 kg Dosing Group Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort	3 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SC Abatacept Ages 6 to 17 n=172 Participants 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).	25 to <50 kg Dosing Group n=46 Participants Weight-tiered dosing group received 87.5 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly.	>=50 kg Dosing Group Weight-tiered dosing group received 125 mg SC abatacept administered to 6 to 17 year old participants by PFS once weekly
Number of Participants With Positive Immunogenicity Response in the Cumulative Period	8 Participants	7 Participants	—

Adverse Events

SC Abatacept Ages 6 to 17

Serious events: 18 serious events

Other events: 127 other events

Deaths: 0 deaths

SC Abatacept Ages 2 to 5

Serious events: 6 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please Email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER