Safety and Efficacy Study of Etanercept (Enbrel®) In Children With Systemic Onset Juvenile Rheumatoid Arthritis

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00078806
• Collaborator: Immunex Corporation (Industry)
• Enrollment: 19
• Arms: 4
• Actual Duration (Months): 35.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Juvenile Rheumatoid Arthritis	Drug: Etanercept; Drug: Placebo	Phase 3

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 Participants who did not meet the response criteria in Part 1A or Part 1B of the study were to be withdrawn from the study as non-responders.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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Safety and Efficacy Study of Etanercept In Children With Systemic Onset Juvenile Rheumatoid Arthritis
• Actual Study Start Date: Jun 4, 2001
• Actual Primary Completion Date: May 6, 2004
• Actual Study Completion Date: May 6, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Etanercept; Administered by subcutaneous injection twice a week; Other Names: Enbrel
Placebo Comparator: Part 2: Placebo Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Drug: Placebo; Administered by subcutaneous injection twice a week
Experimental: Part 2: Etanercept Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.	Drug: Etanercept; Administered by subcutaneous injection twice a week; Other Names: Enbrel
Experimental: Part 3: Participants who experienced a flare or completed 3 months of treatment in Part 2 entered Part 3 and received open-label treatment with etanercept at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to a maximum of 12 months, including treatment in Part 2.	Drug: Etanercept; Administered by subcutaneous injection twice a week; Other Names: Enbrel

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.]

2. 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.

3. 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).

4. 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).

5. 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).

6. 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).

7. 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.

8. 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.

9. 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]

10. Change From Baseline in Number of Joints With Limitation of Motion in Part 2 [Baseline and months 5, 6, 7, 8, and 9]

11. 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).

12. 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).

13. 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]

14. Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 [Baseline and months 5, 6, 7, 8, and 9]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen
• Immunex Corporation

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results
• To access clinical trial results information click on this link
• FDA-approved Drug Labeling

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00078806
• Other Study ID Numbers: 20021631; NCT00039949
• First Posted: Mar 9, 2004
• Last Update Posted: Sep 25, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Amgen: Systemic Onset Juvenile Rheumatoid Arthritis; SOJRA; Fever; Rash; Joint Pain
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Arthritis, Juvenile; Etanercept

Study Results

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 Detail	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.

Arm/Group Title	Part 1: Etanercept	Part 2: Placebo	Part 2: Etanercept	Part 3: Etanercept
Arm/Group Description	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.	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.	Participants who experienced a flare in Part 2 or completed 3 months of treatment in Part 2 entered Part 3 and received open-label treatment with etanercept at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to a maximum of 12 months, including Part 2.
Period Title: Part 1A
STARTED	19	0	0	0
COMPLETED	9	0	0	0
NOT COMPLETED	10	0	0	0
Period Title: Part 1A
STARTED	10	0	0	0
COMPLETED	2	0	0	0
NOT COMPLETED	8	0	0	0
Period Title: Part 1A
STARTED	0	6	4	0
Received Study Drug	0	5	4	0
COMPLETED	0	5	4	0
NOT COMPLETED	0	1	0	0
Period Title: Part 1A
STARTED	0	0	0	9
COMPLETED	0	0	0	9
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.05 (4.20)
Sex: Female, Male (Count of Participants)
Female	10 52.6%
Male	9 47.4%
Race/Ethnicity, Customized (Count of Participants)
White	15 78.9%
Hispanic	2 10.5%
Other	2 10.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Part 2 With Disease Flare
Description	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)

Outcome Measure Data

Analysis Population Description

Participants randomized into Part 2 who received at least 1 dose of study drug in Part 2 (placebo or etanercept).

Arm/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Count of Participants [Participants]	1 5.3%	0 NaN

2. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Participants who entered each part of the study and received study drug in each part of the study.

Arm/Group Title	Part 1A: Etanercept 0.4 mg/kg	Part 1B: Etanercept 0.8 mg/kg	Part 2: Placebo	Part 2: Etanercept	Part 3: Etanercept
Arm/Group Description	Participants received 0.4 mg/kg etanercept administered subcutaneously twice a week for up to 6 months in Part 1A.	Participants in Part A1 who had a partial response entered Part 1B and received 0.8 mg/kg etanercept twice weekly for up to 4 months.	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.	Participants who experienced a flare in Part 2 or completed 3 months of treatment in Part 2 entered Part 3 and received open-label treatment with etanercept at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to a maximum of 12 months, including Part 2.
Measure Participants	19	8	5	4	9
Non-infectious adverse events	16 84.2%	3 NaN	2 NaN	2 NaN	4 NaN
Infectious adverse events	14 73.7%	2 NaN	4 NaN	1 NaN	3 NaN

3. Secondary Outcome

Title	Time to Flare in Part 2
Description	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)

Outcome Measure Data

Analysis Population Description

Participants randomized in Part 2 with a flare in Part 2

Arm/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	1	0
Median (Full Range) [days]	180

4. Secondary Outcome

Title	Change From Baseline in Physician Global Assessment of Disease Severity in Part 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	19
Month 1	-1.42 (2.34)
Month 2	-2.21 (2.57)
Month 3	-1.26 (2.62)
Month 4	-1.82 (2.53)
Month 5	-2.13 (2.36)
Month 6	-1.64 (2.58)
Month 7	-0.40 (1.82)
Month 8	0.50 (2.12)
Month 9	0.00 (1.41)

5. Secondary Outcome

Title	Change From Baseline in Physician Global Assessment of Disease Severity in Part 2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	-1.00 (NA)	-4.00 (NA)
Month 6	-0.50 (2.12)	-3.00 (1.41)
Month 7	-3.67 (1.53)	-4.25 (0.50)
Month 8	-4.00 (1.83)	-2.67 (2.52)
Month 9	-4.67 (1.53)	-6.00 (NA)

6. Secondary Outcome

Title	Change From Baseline in Patient's/Parent's Global Assessment in Part 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	18
Month 1	-1.88 (2.52)
Month 2	-2.38 (2.63)
Month 3	-1.44 (3.46)
Month 4	-2.50 (2.62)
Month 5	-2.54 (2.93)
Month 6	-2.89 (2.09)
Month 7	-2.00 (3.32)
Month 8	-0.50 (0.71)
Month 9	0.00 (NA)

7. Secondary Outcome

Title	Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	0.00 (NA)	-7.00 (NA)
Month 6	-3.00 (4.24)	-5.00 (2.83)
Month 7	-3.33 (0.58)	-4.25 (1.89)
Month 8	-4.25 (2.22)	-2.67 (2.31)
Month 9	-5.33 (0.58)	-5.00 (NA)

8. Secondary Outcome

Title	Change From Baseline in Number of Active Joints in Part 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	18
Month 1	-1.94 (6.65)
Month 2	-6.75 (10.35)
Month 3	-3.50 (18.89)
Month 4	-3.21 (5.42)
Month 5	-5.46 (9.20)
Month 6	-1.55 (8.72)
Month 7	-1.83 (5.19)
Month 8	-1.67 (8.08)
Month 9	-4.00 (4.24)

9. Secondary Outcome

Title	Change From Baseline in Number of Active Joints in Part 2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	-12.00 (NA)
Month 6	-11.50 (7.78)	-11.00 (12.73)
Month 7	-6.33 (4.51)	-17.00 (9.90)
Month 8	-4.67 (2.08)	-13.00 (5.00)
Month 9	-25.00 (NA)

10. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	18
Month 1	0.50 (7.34)
Month 2	-0.19 (6.49)
Month 3	1.88 (15.11)
Month 4	1.27 (7.71)
Month 5	-0.92 (3.78)
Month 6	2.56 (7.06)
Month 7	-0.40 (6.15)
Month 8	-1.33 (7.64)
Month 9	-5.50 (6.36)

11. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	4.0 (NA)	-2.00 (NA)
Month 6	4.50 (2.12)	26.00 (NA)
Month 7	2.67 (4.73)	-3.00 (5.94)
Month 8	1.75 (4.86)	1.00 (8.19)
Month 9	-8.00 (13.89)

12. Secondary Outcome

Title	Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	19
Month 1	-0.35 (0.74)
Month 2	-0.30 (0.68)
Month 3	-0.27 (0.72)
Month 4	-0.29 (0.73)
Month 5	-0.47 (0.84)
Month 6	-0.57 (1.15)
Month 7	-0.29 (0.66)
Month 8	-0.06 (1.50)
Month 9	0.25 (1.06)

13. Secondary Outcome

Title	Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	0.0 (NA)	-1.63 (NA)
Month 6	-0.06 (0.09)	-0.75 (1.24)
Month 7	-1.08 (1.23)	-0.63 (1.18)
Month 8	-1.09 (1.19)	-0.29 (0.56)
Month 9	-1.54 (1.44)	-1.50 (NA)

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 1: Etanercept
Arm/Group Description	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.
Measure Participants	6
Month 1	-4.13 (6.10)
Month 2	-4.23 (9.53)
Month 3	-4.04 (6.80)
Month 4	-6.03 (7.66)
Month 5	-3.07 (3.71)
Month 6	-5.97 (NA)

15. Secondary Outcome

Title	Change From Baseline in C-reactive Protein (CRP) Levels in Part 2
Time Frame	Baseline and months 5, 6, 7, 8, and 9

Outcome Measure Data

Analysis Population Description

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/Group Title	Part 2: Placebo	Part 2: Etanercept
Arm/Group Description	Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.	Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months.
Measure Participants	5	4
Month 5	-0.44 (NA)
Month 6	1.88 (NA)	-0.77 (NA)
Month 7	-3.43 (3.60)
Month 8	-3.43 (3.60)
Month 9	-5.97 (NA)

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 one month after the last dose of study drug.
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Part 1A: Etanercept 0.4 mg/kg		Part 1B: Etanercept 0.8 mg/kg		Part 2: Placebo		Part 2: Etanercept 0.4/0.8 mg/kg		Part 3: Etanercept 0.4/0.8 mg/kg
Arm/Group Description	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 in Part 1A entered Part 1B and received 0.8 mg/kg etanercept twice weekly for up to 4 months.		Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months in Part 2.		Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months in Part 2.		Participants who experienced a flare or completed 3 months of treatment in Part 2 entered Part 3 and received open-label treatment with etanercept at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to a maximum of 12 months, including treatment received in Part 2.
All Cause Mortality
	Part 1A: Etanercept 0.4 mg/kg		Part 1B: Etanercept 0.8 mg/kg		Part 2: Placebo		Part 2: Etanercept 0.4/0.8 mg/kg		Part 3: Etanercept 0.4/0.8 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1A: Etanercept 0.4 mg/kg		Part 1B: Etanercept 0.8 mg/kg		Part 2: Placebo		Part 2: Etanercept 0.4/0.8 mg/kg		Part 3: Etanercept 0.4/0.8 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		1/8 (12.5%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Infections and infestations
Gastroenteritis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Pleurisy	0/19 (0%)		1/8 (12.5%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Part 1A: Etanercept 0.4 mg/kg		Part 1B: Etanercept 0.8 mg/kg		Part 2: Placebo		Part 2: Etanercept 0.4/0.8 mg/kg		Part 3: Etanercept 0.4/0.8 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)		4/8 (50%)		4/5 (80%)		3/4 (75%)		5/9 (55.6%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Ear and labyrinth disorders
Ear pain	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Eye disorders
Cataract	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Abdominal pain upper	3/19 (15.8%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Aphthous ulcer	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Cheilosis	1/19 (5.3%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		0/9 (0%)
Diarrhoea	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		1/4 (25%)		0/9 (0%)
Nausea	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Vomiting	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
General disorders
Fatigue	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Feeling hot	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Injection site bruising	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Injection site erythema	3/19 (15.8%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Injection site pruritus	3/19 (15.8%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Injection site rash	1/19 (5.3%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		0/9 (0%)
Injection site reaction	7/19 (36.8%)		0/8 (0%)		0/5 (0%)		1/4 (25%)		2/9 (22.2%)
Immune system disorders
Drug hypersensitivity	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Infections and infestations
Bronchitis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Conjunctivitis	0/19 (0%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Epstein-Barr viraemia	0/19 (0%)		1/8 (12.5%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Herpes simplex	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Herpes zoster	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Influenza	0/19 (0%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Nasopharyngitis	0/19 (0%)		0/8 (0%)		0/5 (0%)		1/4 (25%)		0/9 (0%)
Oral herpes	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Otitis media	1/19 (5.3%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		0/9 (0%)
Paronychia	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Pharyngitis	1/19 (5.3%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		0/9 (0%)
Pharyngitis streptococcal	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Sinusitis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Upper respiratory tract infection	6/19 (31.6%)		2/8 (25%)		2/5 (40%)		0/4 (0%)		2/9 (22.2%)
Urinary tract infection	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Viral infection	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Injury, poisoning and procedural complications
Fall	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Spinal fracture	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Thermal burn	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Tooth injury	0/19 (0%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Investigations
Haemoglobin decreased	0/19 (0%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthritis	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Costochondritis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Flank pain	0/19 (0%)		1/8 (12.5%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Osteopenia	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Rheumatoid arthritis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Nervous system disorders
Dizziness	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Headache	6/19 (31.6%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/19 (10.5%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Epistaxis	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Nasal congestion	1/19 (5.3%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Purpura	0/19 (0%)		0/8 (0%)		0/5 (0%)		0/4 (0%)		1/9 (11.1%)
Skin lesion	0/19 (0%)		0/8 (0%)		1/5 (20%)		0/4 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.