Juvenile Rheumatoid Arthritis
Conditions
Keywords
Systemic Onset Juvenile Rheumatoid Arthritis, SOJRA, Fever, Rash, Joint Pain
Brief summary
The primary objective of this study was to determine the efficacy of etanercept in pediatric patients with systemically active system onset juvenile rheumatoid arthritis (SOJRA).
Detailed description
Participants were to receive etanercept at a dose of 0.4 mg/kg twice weekly in Part 1A. Participants who had a partial response (not able to reduce prednisone dose by 50% of the baseline dose in 5 months) while on 0.4 mg/kg twice weekly etanercept in Part 1A were to enter Part 1B for up to 4 months and were to have the dose of etanercept increased to 0.8 mg/kg twice weekly. Participants who did not meet the response criteria in Part 1A or Part 1B of the study were to be withdrawn from the study as non-responders. Participants who responded in either Part 1A or Part 1B were randomized into Part 2, where they received etanercept or matching placebo in a double-blind manner twice weekly for up to 3 months. In Part 2, participants were stratified by the dosage of etanercept (0.4 mg/kg or 0.8 mg/kg) they were receiving in Part 1A or Part 1B. Participants could enter Part 3, the open-label re-treatment portion of the study, only if they had been entered into Part 2 of the study and had either flared in Part 2 or had completed 3 months of treatment in Part 2. The maximum time participants could receive etanercept in Part 2 and Part 3 combined was 12 months.
Interventions
DRUGEtanercept
Administered by subcutaneous injection twice a week
DRUGPlacebo
Administered by subcutaneous injection twice a week
Sponsors
Immunex Corporation
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* 2 - 18 years of age * SOJRA for at least 3 months, with stable systemic features * If taking methotrexate, hydroxychloroquine, or NSAIDs, dose must be stable * Must take prednisone at a stable dose
Exclusion criteria
* Need for other DMARDs or prestudy requirements for oral or parenteral pulse steroids or intra-articular steroids * Pregnant or nursing female * Clinically significant abnormal laboratory test results for blood cells, liver or kidney function, or serology * Previous receipt of any tumor necrosis factor (TNF) inhibitor * Live virus vaccine within 12 weeks of study entry * Participation in another study requiring informed consent within 12 weeks of entry * Diabetes that requires insulin treatment * Infection, chronic, recurrent, or currently active * Any serious medical or psychiatric condition or history of alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Part 2 With Disease Flare | 3 months during Part 2 (depending on the timing of response, entry into Part 2 was between study months 3 and 10) | Disease flare was defined as the presence of: * 1 major flare criterion plus 1 minor flare criterion or 1 lab criterion, OR * 2 minor flare criteria plus 2 lab criteria Major Criteria: * Fever of SOJRA, defined as a spike in axillary temperature ≥ 100°F (38°C) for ≥ 2 days per week in the prior 2 weeks or 8 days during the prior month * Symptomatic serositis documented by x-ray or other imaging modality Minor Flare Criteria * Rash of SOJRA, documented in the daily diary * Splenomegaly defined as spleen palpable \> 2 cm below the left costal margin * Lymphadenopathy defined as ≥ 1 cm in \> 1 node area * Arthritis defined as ≥ 2 active joints with swelling not due to deformity, or if swelling is absent, then 2 joints with loss of motion with pain on passive motion and/or warmth. Laboratory Criteria: All labs should be outside the normal range and with 30% worsening: * Albumin * Platelet count * Hemoglobin * C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Flare in Part 2 | From first dose in Part 1 to the end of Part 2 (up to 13 months) | Time to flare was defined as the time from first dose of etanercept in Part 1 to the date of flare during Part 2. |
| Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). |
| Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). |
| Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). |
| Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). |
| Change From Baseline in Number of Active Joints in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth. |
| Number of Participants With Adverse Events | Part 1A, maximum duration on treatment was 207 days; Part 1B, maximum duration on treatment was 120 days; Part 2, maximum duration on treatment was 88 days; Part 3, maximum duration on treatment was 130 days; plus 30 days after last dose of study drug. | — |
| Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | — |
| Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | — |
| Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do). |
| Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do). |
| Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | — |
| Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | — |
| Change From Baseline in Number of Active Joints in Part 2 | Baseline and months 5, 6, 7, 8, and 9 | Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth. |
Participant flow
Recruitment details
Participants with systemic onset juvenile rheumatoid arthritis (SOJRA) were enrolled at 7 sites in the United States and 4 sites in Canada.
Pre-assignment details
Participants who responded in Part 1A or 1B were randomized into Part 2, stratified by the dosage of etanercept (0.4 mg/kg or 0.8 mg/kg) they received in Part 1. Participants entered Part 3 only if they had either flared in Part 2 or had completed 3 months of treatment in Part 2. Participants who did not respond in Part 1A or 1B were withdrawn.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Etanercept Participants received 0.4 mg/kg etanercept administered subcutaneously twice a week for up to 6 months in Part 1A.
Participants who had a partial response entered Part 1B and received 0.8 mg/kg etanercept twice weekly for up to 4 months. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1A | Adverse Event | 2 | 0 | 0 | 0 |
| Part 1A | Lack of Efficacy | 7 | 0 | 0 | 0 |
| Part 1A | Other | 1 | 0 | 0 | 0 |
| Part 1B | Adverse Event | 1 | 0 | 0 | 0 |
| Part 1B | Lack of Efficacy | 7 | 0 | 0 | 0 |
| Part 2 | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Etanercept |
|---|---|
| Age, Continuous | 9.05 years STANDARD_DEVIATION 4.2 |
| Race/Ethnicity, Customized Hispanic | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 15 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 19 | 4 / 8 | 4 / 5 | 3 / 4 | 5 / 9 |
| serious Total, serious adverse events | 3 / 19 | 1 / 8 | 0 / 5 | 0 / 4 | 0 / 9 |
Outcome results
Primary
Number of Participants in Part 2 With Disease Flare
Disease flare was defined as the presence of: * 1 major flare criterion plus 1 minor flare criterion or 1 lab criterion, OR * 2 minor flare criteria plus 2 lab criteria Major Criteria: * Fever of SOJRA, defined as a spike in axillary temperature ≥ 100°F (38°C) for ≥ 2 days per week in the prior 2 weeks or 8 days during the prior month * Symptomatic serositis documented by x-ray or other imaging modality Minor Flare Criteria * Rash of SOJRA, documented in the daily diary * Splenomegaly defined as spleen palpable \> 2 cm below the left costal margin * Lymphadenopathy defined as ≥ 1 cm in \> 1 node area * Arthritis defined as ≥ 2 active joints with swelling not due to deformity, or if swelling is absent, then 2 joints with loss of motion with pain on passive motion and/or warmth. Laboratory Criteria: All labs should be outside the normal range and with 30% worsening: * Albumin * Platelet count * Hemoglobin * C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)
Time frame: 3 months during Part 2 (depending on the timing of response, entry into Part 2 was between study months 3 and 10)
Population: Participants randomized into Part 2 who received at least 1 dose of study drug in Part 2 (placebo or etanercept).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2: Placebo | Number of Participants in Part 2 With Disease Flare | 1 Participants |
| Part 2: Etanercept | Number of Participants in Part 2 With Disease Flare | 0 Participants |
Secondary
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1
Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do).
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 1 | -0.35 units on a scale | Standard Deviation 0.74 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 2 | -0.30 units on a scale | Standard Deviation 0.68 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 3 | -0.27 units on a scale | Standard Deviation 0.72 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 7 | -0.29 units on a scale | Standard Deviation 0.66 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 8 | -0.06 units on a scale | Standard Deviation 1.5 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 9 | 0.25 units on a scale | Standard Deviation 1.06 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 4 | -0.29 units on a scale | Standard Deviation 0.73 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 5 | -0.47 units on a scale | Standard Deviation 0.84 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Month 6 | -0.57 units on a scale | Standard Deviation 1.15 |
Secondary
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2
Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do).
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 6 | -0.06 units on a scale | Standard Deviation 0.09 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 8 | -1.09 units on a scale | Standard Deviation 1.19 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 7 | -1.08 units on a scale | Standard Deviation 1.23 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 9 | -1.54 units on a scale | Standard Deviation 1.44 |
| Part 2: Placebo | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 5 | 0.0 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 9 | -1.50 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 5 | -1.63 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 6 | -0.75 units on a scale | Standard Deviation 1.24 |
| Part 2: Etanercept | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 7 | -0.63 units on a scale | Standard Deviation 1.18 |
| Part 2: Etanercept | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Month 8 | -0.29 units on a scale | Standard Deviation 0.56 |
Secondary
Change From Baseline in C-reactive Protein (CRP) Levels in Part 1
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 3 | -4.04 mg/dL | Standard Deviation 6.8 |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 4 | -6.03 mg/dL | Standard Deviation 7.66 |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 5 | -3.07 mg/dL | Standard Deviation 3.71 |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 6 | -5.97 mg/dL | — |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 1 | -4.13 mg/dL | Standard Deviation 6.1 |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 | Month 2 | -4.23 mg/dL | Standard Deviation 9.53 |
Secondary
Change From Baseline in C-reactive Protein (CRP) Levels in Part 2
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 5 | -0.44 mg/dL | — |
| Part 2: Placebo | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 6 | 1.88 mg/dL | — |
| Part 2: Etanercept | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 6 | -0.77 mg/dL | — |
| Part 2: Etanercept | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 7 | -3.43 mg/dL | Standard Deviation 3.6 |
| Part 2: Etanercept | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 8 | -3.43 mg/dL | Standard Deviation 3.6 |
| Part 2: Etanercept | Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 | Month 9 | -5.97 mg/dL | — |
Secondary
Change From Baseline in Number of Active Joints in Part 1
Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth.
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 1 | -1.94 active joints | Standard Deviation 6.65 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 2 | -6.75 active joints | Standard Deviation 10.35 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 3 | -3.50 active joints | Standard Deviation 18.89 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 4 | -3.21 active joints | Standard Deviation 5.42 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 5 | -5.46 active joints | Standard Deviation 9.2 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 6 | -1.55 active joints | Standard Deviation 8.72 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 7 | -1.83 active joints | Standard Deviation 5.19 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 8 | -1.67 active joints | Standard Deviation 8.08 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 1 | Month 9 | -4.00 active joints | Standard Deviation 4.24 |
Secondary
Change From Baseline in Number of Active Joints in Part 2
Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth.
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 2 | Month 5 | -12.00 active joints | — |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 2 | Month 6 | -11.50 active joints | Standard Deviation 7.78 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 2 | Month 7 | -6.33 active joints | Standard Deviation 4.51 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 2 | Month 8 | -4.67 active joints | Standard Deviation 2.08 |
| Part 2: Placebo | Change From Baseline in Number of Active Joints in Part 2 | Month 9 | -25.00 active joints | — |
| Part 2: Etanercept | Change From Baseline in Number of Active Joints in Part 2 | Month 6 | -11.00 active joints | Standard Deviation 12.73 |
| Part 2: Etanercept | Change From Baseline in Number of Active Joints in Part 2 | Month 8 | -13.00 active joints | Standard Deviation 5 |
| Part 2: Etanercept | Change From Baseline in Number of Active Joints in Part 2 | Month 7 | -17.00 active joints | Standard Deviation 9.9 |
Secondary
Change From Baseline in Number of Joints With Limitation of Motion in Part 1
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 3 | 1.88 joints | Standard Deviation 15.11 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 4 | 1.27 joints | Standard Deviation 7.71 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 5 | -0.92 joints | Standard Deviation 3.78 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 6 | 2.56 joints | Standard Deviation 7.06 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 8 | -1.33 joints | Standard Deviation 7.64 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 1 | 0.50 joints | Standard Deviation 7.34 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 2 | -0.19 joints | Standard Deviation 6.49 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 7 | -0.40 joints | Standard Deviation 6.15 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 1 | Month 9 | -5.50 joints | Standard Deviation 6.36 |
Secondary
Change From Baseline in Number of Joints With Limitation of Motion in Part 2
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 7 | 2.67 joints | Standard Deviation 4.73 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 6 | 4.50 joints | Standard Deviation 2.12 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 8 | 1.75 joints | Standard Deviation 4.86 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 9 | -8.00 joints | Standard Deviation 13.89 |
| Part 2: Placebo | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 5 | 4.0 joints | — |
| Part 2: Etanercept | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 8 | 1.00 joints | Standard Deviation 8.19 |
| Part 2: Etanercept | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 5 | -2.00 joints | — |
| Part 2: Etanercept | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 6 | 26.00 joints | — |
| Part 2: Etanercept | Change From Baseline in Number of Joints With Limitation of Motion in Part 2 | Month 7 | -3.00 joints | Standard Deviation 5.94 |
Secondary
Change From Baseline in Patient's/Parent's Global Assessment in Part 1
Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 8 | -0.50 units on a scale | Standard Deviation 0.71 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 9 | 0.00 units on a scale | — |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 1 | -1.88 units on a scale | Standard Deviation 2.52 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 2 | -2.38 units on a scale | Standard Deviation 2.63 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 3 | -1.44 units on a scale | Standard Deviation 3.46 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 4 | -2.50 units on a scale | Standard Deviation 2.62 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 5 | -2.54 units on a scale | Standard Deviation 2.93 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 6 | -2.89 units on a scale | Standard Deviation 2.09 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Month 7 | -2.00 units on a scale | Standard Deviation 3.32 |
Secondary
Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2
Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 8 | -4.25 units on a scale | Standard Deviation 2.22 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 9 | -5.33 units on a scale | Standard Deviation 0.58 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 7 | -3.33 units on a scale | Standard Deviation 0.58 |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 5 | 0.00 units on a scale | — |
| Part 2: Placebo | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 6 | -3.00 units on a scale | Standard Deviation 4.24 |
| Part 2: Etanercept | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 5 | -7.00 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 8 | -2.67 units on a scale | Standard Deviation 2.31 |
| Part 2: Etanercept | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 7 | -4.25 units on a scale | Standard Deviation 1.89 |
| Part 2: Etanercept | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 9 | -5.00 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Month 6 | -5.00 units on a scale | Standard Deviation 2.83 |
Secondary
Change From Baseline in Physician Global Assessment of Disease Severity in Part 1
Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Time frame: Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
Population: Participants who enrolled in the study and received at least one dose of etanercept in Part 1A or Part 1B and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 1 | -1.42 units on a scale | Standard Deviation 2.34 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 2 | -2.21 units on a scale | Standard Deviation 2.57 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 3 | -1.26 units on a scale | Standard Deviation 2.62 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 4 | -1.82 units on a scale | Standard Deviation 2.53 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 5 | -2.13 units on a scale | Standard Deviation 2.36 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 6 | -1.64 units on a scale | Standard Deviation 2.58 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 7 | -0.40 units on a scale | Standard Deviation 1.82 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 8 | 0.50 units on a scale | Standard Deviation 2.12 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Month 9 | 0.00 units on a scale | Standard Deviation 1.41 |
Secondary
Change From Baseline in Physician Global Assessment of Disease Severity in Part 2
Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Time frame: Baseline and months 5, 6, 7, 8, and 9
Population: Participants who randomized and received at least one dose of study drug in Part 2 and with available data at each time point; participants could join Part 2 at different times depending on their response status.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 6 | -0.50 units on a scale | Standard Deviation 2.12 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 8 | -4.00 units on a scale | Standard Deviation 1.83 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 7 | -3.67 units on a scale | Standard Deviation 1.53 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 9 | -4.67 units on a scale | Standard Deviation 1.53 |
| Part 2: Placebo | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 5 | -1.00 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 9 | -6.00 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 5 | -4.00 units on a scale | — |
| Part 2: Etanercept | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 6 | -3.00 units on a scale | Standard Deviation 1.41 |
| Part 2: Etanercept | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 7 | -4.25 units on a scale | Standard Deviation 0.5 |
| Part 2: Etanercept | Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Month 8 | -2.67 units on a scale | Standard Deviation 2.52 |
Secondary
Number of Participants With Adverse Events
Time frame: Part 1A, maximum duration on treatment was 207 days; Part 1B, maximum duration on treatment was 120 days; Part 2, maximum duration on treatment was 88 days; Part 3, maximum duration on treatment was 130 days; plus 30 days after last dose of study drug.
Population: Participants who entered each part of the study and received study drug in each part of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 2: Placebo | Number of Participants With Adverse Events | Infectious adverse events | 14 Participants |
| Part 2: Placebo | Number of Participants With Adverse Events | Non-infectious adverse events | 16 Participants |
| Part 2: Etanercept | Number of Participants With Adverse Events | Infectious adverse events | 2 Participants |
| Part 2: Etanercept | Number of Participants With Adverse Events | Non-infectious adverse events | 3 Participants |
| Part 2: Placebo | Number of Participants With Adverse Events | Non-infectious adverse events | 2 Participants |
| Part 2: Placebo | Number of Participants With Adverse Events | Infectious adverse events | 4 Participants |
| Part 2: Etanercept | Number of Participants With Adverse Events | Infectious adverse events | 1 Participants |
| Part 2: Etanercept | Number of Participants With Adverse Events | Non-infectious adverse events | 2 Participants |
| Part 3: Etanercept | Number of Participants With Adverse Events | Non-infectious adverse events | 4 Participants |
| Part 3: Etanercept | Number of Participants With Adverse Events | Infectious adverse events | 3 Participants |
Secondary
Time to Flare in Part 2
Time to flare was defined as the time from first dose of etanercept in Part 1 to the date of flare during Part 2.
Time frame: From first dose in Part 1 to the end of Part 2 (up to 13 months)
Population: Participants randomized in Part 2 with a flare in Part 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2: Placebo | Time to Flare in Part 2 | 180 days |