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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

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Active Polyarticular Juvenile Idiopathic Arthritis
Intervention Biological: Abatacept
Enrollment 187
Recruitment Details  
Pre-assignment Details 187 participants (ages 6 to 17) were enrolled and 173 were treated during the short-term (ST) period. Reasons for not being treated include 5 withdrew consent, 1 was non-compliant and 8 no longer met the study criteria. 164 completed the ST period. 157 entered the long-term extension (LTE) period. 149 participants are in the LTE on-going study.
Arm/Group Title SC Abatacept Ages 6 to 17
Hide Arm/Group Description Subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to the following weight-tiered dosing regimen: 10 to < 25kg (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).
Period Title: Short-Term (ST) Period
Started 173
Completed 164
Not Completed 9
Reason Not Completed
Adverse Event             3
Lack of Efficacy             3
Withdrawal of Consent             2
Poor/Non-Compliance             1
Period Title: Long-Term Extension
Started 157 [1]
Completed 0 [2]
Not Completed 157
Reason Not Completed
Lack of Efficacy             6
Adverse Event             1
No Longer Met Study Criteria             1
Still in On-Going Study             149
[1]
7 participants completed ST but did not continue in study.
[2]
Study is on-going
Arm/Group Title SC Abatacept Ages 6 to 17
Hide Arm/Group Description Subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Baseline Participants 173
Hide Baseline Analysis Population Description
All treated participants 6 to17 years of age
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 173 participants
13.0
(6.0 to 17.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 173 participants
Female
136
  78.6%
Male
37
  21.4%
Weight  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants
<25 kg 18
25 to 50 kg 74
>=50 kg 81
1.Primary Outcome
Title Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17, with evaluable PK concentration data
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
Overall Number of Participants Analyzed 131
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
39.7
(35%)
2.Secondary Outcome
Title Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30)
Hide Description 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.
Time Frame Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, ages 6 to 17
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 173
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
80.9
(75.1 to 86.8)
3.Secondary Outcome
Title Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17
Hide Description 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).
Time Frame Days 57, 85 and 113
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17, with PK-evaluable concentration data
Arm/Group Title 10 to <25 kg Dosing Group 25 to <50 kg Dosing Group >=50 kg Dosing Group
Hide Arm/Group Description:
Weight-tiered dosing group receiving 50 milligrams (mg) subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
Weight-tiered dosing group receiving 87.5 mg subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
Weight-tiered dosing group receiving 125 mg subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
Overall Number of Participants Analyzed 17 69 74
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (µg/mL)
Day 57 (n=14,69,74)
29.5
(32%)
36.2
(35%)
33.3
(33%)
Day 85 (n=17,63,65)
27.7
(38%)
42.5
(32%)
36.0
(40%)
Day 113 (n=15,61,55)
34.3
(39%)
44.2
(34%)
36.3
(31%)
4.Secondary Outcome
Title 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
Hide Description

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.

Time Frame Day 1 up to 56 days after last dose up to March 2015
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 173
Measure Type: Number
Unit of Measure: participants
Deaths 0
SAEs 5
Drug-Related SAEs 1
Discontinuation due to SAEs 2
Drug-Related AEs 36
Discontinuation due to AEs 3
5.Secondary Outcome
Title Number of Participants (Ages 6 to 17) With Adverse Events (AEs) of Special Interest in the Short Term Period
Hide Description

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.

Time Frame Day 1 up to 56 days after last dose up to March 2015
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 173
Measure Type: Number
Unit of Measure: participants
Malignancies 1
Autoimmune Disorders 2
Local Injection-Site Reactions 9
AEs within 24 Hours of Drug Administration 42
Infections 55
6.Secondary Outcome
Title Number of Participants (Ages 6 to 17) With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period
Hide Description

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.

Time Frame Day 1 up to 56 days after last dose up to March 2015
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
Overall Number of Participants Analyzed 173
Measure Type: Number
Unit of Measure: participants
Deaths 0
SAEs 8
Drug-Related SAEs 1
Discontinuation Due to SAEs 2
Treatment-Related AEs 45
Discontinuation Due to AEs 4
7.Secondary Outcome
Title Number of Participants (Ages 6 to 17) With Adverse Events (AEs) of Special Interest in the Cumulative Period
Hide Description

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.

Time Frame Day 1 up to 56 days after last dose, up to March 2015
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants, ages 6 to 17
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 173
Measure Type: Number
Unit of Measure: participants
Malignancies 1
Autoimmune Disorders 3
Local Injection-Site Reactions 10
AEs within 24 Hours of Drug Administration 59
Infections 90
8.Secondary Outcome
Title Number of Participants (Ages 6 to 17) With Positive Immunogenicity Response in the Short Term Period
Hide Description 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.
Time Frame Day 1 to 168 days after the last dose of study medication in the short-term period
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, ages 6 to 17, who received at least one dose of study medication and who had at least one immunogenicity result reported after start of study medication
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 171
Measure Type: Number
Unit of Measure: participants
3
9.Secondary Outcome
Title Number of Participants (Ages 6 to 17) With Positive Immunogenicity Response in the Cumulative Period
Hide Description 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.
Time Frame Day 1 to 6 months following discontinuation of treatment, up to March 2015
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, ages 6 to 17, who received at least one dose of study medication and who had at least one immunogenicity result reported after start of study medication
Arm/Group Title Combined Abatacept Dosing Groups, Ages 6 to 17
Hide Arm/Group Description:
All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered by prefilled syringe (PFS) once weekly according to weight-tiered dose regimen as follows: 10 to < 25kg (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 Number of Participants Analyzed 171
Measure Type: Number
Unit of Measure: participants
4
Time Frame 20 months
Adverse Event Reporting Description Study initiated: June 2013; Study completed: March 2015
 
Arm/Group Title SC Abatacept Ages 6 to 17
Hide Arm/Group Description All weight-tiered dosing groups receiving subcutaneous (SC) abatacept administered to 6 to 17 year old participants by prefilled syringe (PFS) once weekly
All-Cause Mortality
SC Abatacept Ages 6 to 17
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
SC Abatacept Ages 6 to 17
Affected / at Risk (%)
Total   8/173 (4.62%) 
Blood and lymphatic system disorders   
Anaemia  1  1/173 (0.58%) 
Gastrointestinal disorders   
Abdominal pain  1  1/173 (0.58%) 
General disorders   
Chest pain  1  1/173 (0.58%) 
Infections and infestations   
Pyelonephritis  1  1/173 (0.58%) 
Sepsis  1  1/173 (0.58%) 
Injury, poisoning and procedural complications   
Radius fracture  1  1/173 (0.58%) 
Metabolism and nutrition disorders   
Hypomagnesaemia  1  1/173 (0.58%) 
Musculoskeletal and connective tissue disorders   
Synovitis  1  1/173 (0.58%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Ovarian germ cell teratoma stage III  1  1/173 (0.58%) 
Renal and urinary disorders   
Nephrolithiasis  1  1/173 (0.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SC Abatacept Ages 6 to 17
Affected / at Risk (%)
Total   71/173 (41.04%) 
Gastrointestinal disorders   
Vomiting  1  11/173 (6.36%) 
Nausea  1  9/173 (5.20%) 
General disorders   
Pyrexia  1  15/173 (8.67%) 
Infections and infestations   
Upper respiratory tract infection  1  22/173 (12.72%) 
Nasopharyngitis  1  34/173 (19.65%) 
Nervous system disorders   
Headache  1  15/173 (8.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01844518     History of Changes
Other Study ID Numbers: IM101-301
2012-003195-39 ( EudraCT Number )
First Submitted: April 29, 2013
First Posted: May 1, 2013
Results First Submitted: February 23, 2016
Results First Posted: March 24, 2016
Last Update Posted: February 15, 2018