Trial Outcomes & Findings for Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis (NCT NCT03781375)

Last Updated: 2019-08-02

Results Overview

Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 30% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: * Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 * Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 * Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) * Number of joints with limitation of motion * Childhood Health Assessment Questionnaire (CHAQ) * Erythrocyte sedimentation rate (ESR)

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

Baseline and month 6

Results posted on

2019-08-02

Participant Flow

This study was conducted at 7 centers in the United States. The study consisted of a 6-month double-blind treatment period followed by a 6-month open-label period where all participants received etanercept + methotrexate. Early transition to open-label treatment was allowed after 2 months of blinded treatment, for disease flare or lack of response.

Participants were randomized equally into 1 of 2 treatments for the double-blind portion of the study. Randomization was stratified by route of methotrexate administration (oral \[PO\] vs subcutaneous \[SC\]) prior to randomization.

Participant milestones

Participant milestones
Measure	Methotrexate + Placebo Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Double-blind Phase STARTED	12	13
Double-blind Phase Received Study Drug	12	13
Double-blind Phase COMPLETED	5	7
Double-blind Phase NOT COMPLETED	7	6
Open-label Phase STARTED	11	9
Open-label Phase Received Study Drug	10	9
Open-label Phase COMPLETED	8	6
Open-label Phase NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Methotrexate + Placebo Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Double-blind Phase Adverse Event	0	1
Double-blind Phase Lack of Response	6	2
Double-blind Phase Other	1	3
Open-label Phase Protocol Issues	0	1
Open-label Phase Suboptimal Clinical Response	1	0
Open-label Phase Other	2	2

Baseline Characteristics

Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate + Placebo n=12 Participants Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept n=13 Participants Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Total n=25 Participants Total of all reporting groups
Age, Continuous	8.75 years STANDARD_DEVIATION 5.71 • n=5 Participants	11.38 years STANDARD_DEVIATION 3.40 • n=7 Participants	10.12 years STANDARD_DEVIATION 4.75 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Oher	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Methotrexate Dosage Route Orally	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Methotrexate Dosage Route Subcutaneously	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Type of Arthritis at Onset Pauciarticular	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Type of Arthritis at Onset Polyarticular	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Type of Arthritis at Onset Systemic	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and month 6

Population: All randomized participants; participants with missing data are counted as non-responders.

Outcome measures

Outcome measures
Measure	Methotrexate + Placebo n=12 Participants Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept n=13 Participants Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Percentage of Participants With a JRA Response at Month 6	33 percentage of participants	38 percentage of participants

SECONDARY outcome

Timeframe: Baseline and month 6

Population: All randomized participants; participants with missing data were counted as non-responders.

Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 50% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: * Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 * Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 * Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) * Number of joints with limitation of motion * Childhood Health Assessment Questionnaire (CHAQ) * Erythrocyte sedimentation rate (ESR)

Outcome measures

Outcome measures
Measure	Methotrexate + Placebo n=12 Participants Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept n=13 Participants Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Percentage of Participants With a 50% Improvement in JRA DOI at Month 6	25 percentage of participants	38 percentage of participants

SECONDARY outcome

Timeframe: Baseline and month 6

Population: All randomized participants; participants with missing data were counted as non-responders.

Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 70% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: * Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 * Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 * Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) * Number of joints with limitation of motion * Childhood Health Assessment Questionnaire (CHAQ) * Erythrocyte sedimentation rate (ESR)

Outcome measures

Outcome measures
Measure	Methotrexate + Placebo n=12 Participants Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.	Methotrexate + Etanercept n=13 Participants Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Percentage of Participants With a 70% Improvement in JRA DOI at Month 6	8 percentage of participants	38 percentage of participants

Adverse Events

Methotrexate + Placebo (Blinded Phase)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Methotrexate + Etanercept (Blinded Phase)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Methotrexate + Etanercept (Open Label Phase)

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate + Placebo (Blinded Phase) n=12 participants at risk Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months.	Methotrexate + Etanercept (Blinded Phase) n=13 participants at risk Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months.	Methotrexate + Etanercept (Open Label Phase) n=19 participants at risk After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
Infections and infestations Appendicitis	0.00% 0/12 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.7% 1/13 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/13 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • Up to 12 months on-study evaluations plus 1 month follow-up Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER