Juvenile Rheumatoid Arthritis
Conditions
Keywords
Juvenile Rheumatoid Arthritis
Brief summary
To evaluate efficacy, safety and pharmacokinetics of adalimumab in Japanese children with Polyarticular Juvenile Rheumatoid Arthritis
Detailed description
This was an open-label long-term study that was completed following study drug approval in Japan for the treatment of JRA. Data are presented through Week 144 and for the final visit.
Interventions
BIOLOGICALAdalimumab
Adalimumab administered subcutaneously every other week, with dosage determined by body weight at study entry (20 mg for children weighing less than 30 kg, 40 mg for children weighing 30 kg or more).
Sponsors
Eisai Co., Ltd.
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of polyarticular juvenile rheumatoid arthritis (JRA) according to the criteria of the American College on Rheumatology (ACR) * Disease activity inadequately controlled by nonsteroidal anti-inflammatory drugs (NSAIDs) or methotrexate (MTX) * Presence at screening of at least 5 swollen joints (not due to deformity) and at least 3 joints with limitation of passive motion with pain by passive motion or/and pain by pressure (tenderness) * Stable dosage of MTX for at least 12 weeks prior to the screening visit or discontinuation of MTX at least 14 days prior to baseline visit (Day 1) * Discontinuation of disease-modifying antirheumatic drugs (DMARDs) other than MTX at least 28 days before screening visit
Exclusion criteria
* History of inflammatory joint disease other than JRA * Functional class IV JRA by ACR criteria * Clinically significant cardiac disease or laboratory abnormalities * Any subject who is considered by the investigator, for any reason, to be an unsuitable candidate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16 | Week 16 | Response defined as at least 30% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 30% worsening in not more than 1 JRA criterion, compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving PedACR 30/50/70 Responses | Week 2, 4, 8, and 24, every 12 weeks from Week 24 to Week 60, and every 24 weeks from Week 72 to the final visit | — |
| Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 | Week 16 | Response defined as at least 50/70% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 50/70% worsening in not more than 1 JRA criterion compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. |
| Mean Serum Adalimumab Concentration | Week 2, 4, 8, 16, and 24, and every 12 weeks up to Week 60 | Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method based on a double-antigen technique. Concentrations are reported as micrograms per milliliter (mcg/mL). |
| Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) | Week 24 and Week 60 | Serum samples with adalimumab concentration below 2 mcg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 20 ng/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose. |
Countries
Japan
Participant flow
Pre-assignment details
Adalimumab dose was determined by baseline body weight (20 mg for subjects weighing \< 30 kg, 40 mg for subjects weighing 30 kg or more) through Week 14. After Week 16, dose was based on body weight measured at Week 16 and every 12 weeks. Twenty subjects received concomitant methotrexate therapy during the study.
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab Adalimumab administered subcutaneously every other week, with dosage determined by body weight at study entry (20 mg for children weighing less than 30 kg, 40 mg for children weighing 30 kg or more). | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Adalimumab |
|---|---|
| Age, Categorical <=18 years | 25 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 13.0 years STANDARD_DEVIATION 3.38 |
| Region of Enrollment Japan | 25 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 6 / 25 |
Outcome results
Primary
Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16
Response defined as at least 30% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 30% worsening in not more than 1 JRA criterion, compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Time frame: Week 16
Population: The analysis was conducted using the full analysis set (FAS) population, which was defined as all subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16 | 23 Participants |
Secondary
Mean Serum Adalimumab Concentration
Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method based on a double-antigen technique. Concentrations are reported as micrograms per milliliter (mcg/mL).
Time frame: Week 2, 4, 8, 16, and 24, and every 12 weeks up to Week 60
Population: For the 20 mg dose, N = 8 at each timepoint. For the 40 mg dose, N = 17 at Weeks 2 and 4; N = 16 at Weeks 8, 16, and 24; N = 14 at Week 36; N = 15 at Week 48; and N = 14 at Week 60.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 36 | 7.60 mcg/mL | Standard Deviation 7.58 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 48 | 7.97 mcg/mL | Standard Deviation 6.69 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 60 | 11.4 mcg/mL | Standard Deviation 9.87 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 2 | 5.03 mcg/mL | Standard Deviation 1.45 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 4 | 5.63 mcg/mL | Standard Deviation 2.71 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 8 | 8.66 mcg/mL | Standard Deviation 4.41 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 16 | 10.8 mcg/mL | Standard Deviation 6.15 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 24 | 11.9 mcg/mL | Standard Deviation 6.8 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 36 | 12.6 mcg/mL | Standard Deviation 6.44 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 48 | 13.0 mcg/mL | Standard Deviation 8.89 |
| Adalimumab | Mean Serum Adalimumab Concentration | 40 mg dose at Week 60 | 13.1 mcg/mL | Standard Deviation 6.73 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 2 | 5.24 mcg/mL | Standard Deviation 1.74 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 4 | 5.46 mcg/mL | Standard Deviation 5.18 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 8 | 6.15 mcg/mL | Standard Deviation 5.88 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 16 | 5.73 mcg/mL | Standard Deviation 5.26 |
| Adalimumab | Mean Serum Adalimumab Concentration | 20 mg dose at Week 24 | 5.79 mcg/mL | Standard Deviation 6.51 |
Secondary
Number of Subjects Achieving PedACR 30/50/70 Responses
Time frame: Week 2, 4, 8, and 24, every 12 weeks from Week 24 to Week 60, and every 24 weeks from Week 72 to the final visit
Population: The analysis was conducted using the full analysis set (FAS) population (all subjects who received at least 1 dose of study drug) as observed. N=25 at Weeks 2, 4, and the Final Visit; N=24 at Weeks 8, 24, and 36; N=23 at Week 48; N=22 at Week 60; N=19 at Weeks 72 and 96; N=11 at Week 120; and N=5 at Week 144.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 144 | 5 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30- Final Visit | 22 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 2 | 7 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 4 | 13 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 8 | 15 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 24 | 19 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 2 | 15 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 4 | 16 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 8 | 19 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 24 | 21 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 36 | 22 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 48 | 21 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 60 | 20 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 72 | 19 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 96 | 18 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR30 at Week 120 | 11 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 36 | 22 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 48 | 19 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 60 | 20 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 72 | 18 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 96 | 18 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 120 | 11 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50 at Week 144 | 5 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR50- Final Visit | 20 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 2 | 1 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 4 | 7 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 8 | 8 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 24 | 15 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 36 | 19 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 48 | 17 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 60 | 16 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 72 | 15 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 96 | 14 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 120 | 11 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70 at Week 144 | 5 Participants |
| Adalimumab | Number of Subjects Achieving PedACR 30/50/70 Responses | Number of subjects achieving PedACR70- Final Visit | 17 Participants |
Secondary
Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16
Response defined as at least 50/70% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 50/70% worsening in not more than 1 JRA criterion compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Time frame: Week 16
Population: The analysis was conducted using the full analysis set (FAS) population, which was defined as all subjects who received at least one dose of study drug. Missing values were treated as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab | Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 | Number of Subjects Achieving PedACR50 at Week 16 | 22 Participants |
| Adalimumab | Number of Subjects Achieving PedACR50 and PedACR70 Responses at Week 16 | Number of Subjects Achieving PedACR70 at Week 16 | 15 Participants |
Secondary
Number of Subjects Positive for Anti-adalimumab Antibodies (AAA)
Serum samples with adalimumab concentration below 2 mcg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 20 ng/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose.
Time frame: Week 24 and Week 60
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab | Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) | Number of subjects with AAA by Week 24 | 4 Participants |
| Adalimumab | Number of Subjects Positive for Anti-adalimumab Antibodies (AAA) | Number of subjects with AAA by Week 60 | 6 Participants |