Trial Outcomes & Findings for Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA) (NCT NCT03780959)

Last Updated: 2019-08-02

Results Overview

Disease flare was defined as a 30% or greater worsening in three of the six JRA Core Set Criteria and ≥ 30% improvement in one or less of the six JRA Core Set Criteria compared to day 90 and a minimum of two active joints (joints with swelling or limitation of movement plus pain and/or tenderness). The JRA Core Set criteria consisted of: * Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms); * Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms); * Number of active joints; * Number of joints with limitation of motion (LOM) and with pain, tenderness, or both; * Childhood Health Assessment Questionnaire (CHAQ) disability domain; * Erythrocyte sedimentation rate (ESR).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

69 participants

Primary outcome timeframe

End of part 1 (day 90) and months 4 to 7

Results posted on

2019-08-02

Participant Flow

Participants were enrolled at 9 sites in the United States and Canada. The study consisted of an open-label treatment period (part 1) where all participants received 0.4 mg etanercept twice weekly for 3 months, followed by a randomized double-blind treatment period (part 2).

At the end of part 1 participants with disease response were randomized to part 2, with stratification according to study center and number of active joints (≤ 2 vs. \> 2) at the end of month 3.

Participant milestones

Participant milestones
Measure	Part 1: Etanercept 0.4 mg/kg Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.	Part 2: Placebo In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Part 1 STARTED	69	0	0
Part 1 COMPLETED	64	0	0
Part 1 NOT COMPLETED	5	0	0
Part 2 STARTED	0	26	25
Part 2 COMPLETED	0	7	19
Part 2 NOT COMPLETED	0	19	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Etanercept 0.4 mg/kg Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.	Part 2: Placebo In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Part 1 Adverse Event	1	0	0
Part 1 Withdrawal by Subject	1	0	0
Part 1 Withdrawal by Parent/Guardian	1	0	0
Part 1 Response Status	2	0	0
Part 2 Withdrawal by Parent/Guardian	0	1	0
Part 2 Response Status	0	18	6

Baseline Characteristics

Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: End of part 1 (day 90) and months 4 to 7

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Part 2: Placebo n=26 Participants In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg n=25 Participants In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.	Part 2: Etanercept 0.4 mg/kg In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Percentage of Participants With Disease Flare in Part 2	81 percentage of participants	28 percentage of participants	—

SECONDARY outcome

Timeframe: Months 4 to 7

Population: All randomized participants

The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.

Outcome measures

Outcome measures
Measure	Part 2: Placebo n=26 Participants In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg n=25 Participants In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.	Part 2: Etanercept 0.4 mg/kg In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Time to Flare in Part 2	28.0 days Interval 6.0 to 123.0	116.0 days Interval 28.0 to 127.0	—

SECONDARY outcome

Timeframe: Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8).

Population: All participants who received at least one dose of study drug

Outcome measures

Outcome measures
Measure	Part 2: Placebo n=69 Participants In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg n=26 Participants In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.	Part 2: Etanercept 0.4 mg/kg n=25 Participants In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Number of Participants With Adverse Events Noninfectious adverse events	51 Participants	9 Participants	13 Participants
Number of Participants With Adverse Events Injection site reactions	27 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events Infections	43 Participants	8 Participants	15 Participants
Number of Participants With Adverse Events Serious adverse events	1 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events Deaths	0 Participants	0 Participants	0 Participants

Adverse Events

Part 1: Etanercept 0.4 mg/kg

Serious events: 1 serious events

Other events: 59 other events

Deaths: 0 deaths

Part 2: Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part 2: Etanercept 0.4 mg/kg

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Etanercept 0.4 mg/kg n=69 participants at risk Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.	Part 2: Placebo n=26 participants at risk n Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg n=25 participants at risk In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Infections and infestations Gastroenteritis	1.4% 1/69 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/26 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/25 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Abnormal behaviour	0.00% 0/69 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/26 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.0% 1/25 • Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8). 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

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 to1 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

Measure	Part 1: Etanercept 0.4 mg/kg n=69 Participants Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.	Part 2: Placebo n=26 Participants In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.	Part 2: Etanercept 0.4 mg/kg n=25 Participants In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.	Total n=120 Participants Total of all reporting groups
Age, Continuous Part 1	10.5 years STANDARD_DEVIATION 3.9 • n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	10.5 years STANDARD_DEVIATION 3.9 • n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Continuous Part 2	—	12.2 years STANDARD_DEVIATION 3.5 • n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	8.9 years STANDARD_DEVIATION 3.7 • n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	10.6 years STANDARD_DEVIATION 3.9 • n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 1 · 4 - 8 years	25 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	25 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 1 · 9 - 12 years	14 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	14 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 1 · 13 - 17 years	30 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	30 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 2 · 4 - 8 years	—	5 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	13 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	18 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 2 · 9 - 12 years	—	4 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	5 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	9 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized Part 2 · 13 - 17 years	—	17 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	7 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	24 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Sex: Female, Male Part 1 · Female	43 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	43 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Sex: Female, Male Part 1 · Male	26 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	26 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Sex: Female, Male Part 2 · Female	—	15 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	19 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	34 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Sex: Female, Male Part 2 · Male	—	11 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	6 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	17 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 1 · Black	6 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	6 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 1 · White	52 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	52 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 1 · Asian	1 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	1 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 1 · Hispanic	9 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	9 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 1 · Native American	1 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	1 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 2 · Black	—	1 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	3 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	4 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 2 · White	—	23 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	14 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	37 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 2 · Asian	—	0 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	1 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	1 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 2 · Hispanic	—	2 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	6 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	8 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized Part 2 · Native American	—	0 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	1 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	1 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 1 · Pauciarticular	7 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	7 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 1 · Polyarticular	40 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	40 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 1 · Systemic	22 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	—	—	22 Participants n=69 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 2 · Pauciarticular	—	1 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	2 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	3 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 2 · Polyarticular	—	17 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	14 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	31 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Type of Onset of Juvenile Rheumatoid Arthritis (JRA) Part 2 · Systemic	—	8 Participants n=26 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	9 Participants n=25 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.	17 Participants n=51 Participants • Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.