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Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)

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ClinicalTrials.gov Identifier: NCT03780959
Recruitment Status : Completed
First Posted : December 19, 2018
Results First Posted : August 2, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Juvenile Rheumatoid Arthritis
Interventions Drug: Etanercept
Drug: Placebo
Enrollment 69
Recruitment Details 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).
Pre-assignment Details 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.
Arm/Group Title Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Hide Arm/Group Description Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months. In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Period Title: Part 1
Started 69 0 0
Completed 64 0 0
Not Completed 5 0 0
Reason Not Completed
Adverse Event             1             0             0
Withdrawal by Subject             1             0             0
Withdrawal by Parent/Guardian             1             0             0
Response Status             2             0             0
Period Title: Part 2
Started [1] 0 26 25
Completed 0 7 19
Not Completed 0 19 6
Reason Not Completed
Withdrawal by Parent/Guardian             0             1             0
Response Status             0             18             6
[1]
Participants who met response criteria at day 90
Arm/Group Title Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg Total
Hide Arm/Group Description Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months. In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months. Total of all reporting groups
Overall Number of Baseline Participants 69 26 25 120
Hide Baseline Analysis Population Description
Baseline data are included for all enrolled participants in part 1 (69) and all participants who randomized in part 2 (51).
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Part 1 Number Analyzed 69 participants 0 participants 0 participants 69 participants
10.5  (3.9) 10.5  (3.9)
Part 2 Number Analyzed 0 participants 26 participants 25 participants 51 participants
12.2  (3.5) 8.9  (3.7) 10.6  (3.9)
[1]
Measure Analysis Population Description: Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part 1 Number Analyzed 69 participants 0 participants 0 participants 69 participants
4 - 8 years
25
  36.2%
25
  36.2%
9 - 12 years
14
  20.3%
14
  20.3%
13 - 17 years
30
  43.5%
30
  43.5%
Part 2 Number Analyzed 0 participants 26 participants 25 participants 51 participants
4 - 8 years
5
  19.2%
13
  52.0%
18
  35.3%
9 - 12 years
4
  15.4%
5
  20.0%
9
  17.6%
13 - 17 years
17
  65.4%
7
  28.0%
24
  47.1%
[1]
Measure Analysis Population Description: Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part 1 Number Analyzed 69 participants 0 participants 0 participants 69 participants
Female
43
  62.3%
43
  62.3%
Male
26
  37.7%
26
  37.7%
Part 2 Number Analyzed 0 participants 26 participants 25 participants 51 participants
Female
15
  57.7%
19
  76.0%
34
  66.7%
Male
11
  42.3%
6
  24.0%
17
  33.3%
[1]
Measure Analysis Population Description: Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part 1 Number Analyzed 69 participants 0 participants 0 participants 69 participants
Black
6
   8.7%
6
   8.7%
White
52
  75.4%
52
  75.4%
Asian
1
   1.4%
1
   1.4%
Hispanic
9
  13.0%
9
  13.0%
Native American
1
   1.4%
1
   1.4%
Part 2 Number Analyzed 0 participants 26 participants 25 participants 51 participants
Black
1
   3.8%
3
  12.0%
4
   7.8%
White
23
  88.5%
14
  56.0%
37
  72.5%
Asian
0
   0.0%
1
   4.0%
1
   2.0%
Hispanic
2
   7.7%
6
  24.0%
8
  15.7%
Native American
0
   0.0%
1
   4.0%
1
   2.0%
[1]
Measure Analysis Population Description: 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)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Part 1 Number Analyzed 69 participants 0 participants 0 participants 69 participants
Pauciarticular
7
  10.1%
7
  10.1%
Polyarticular
40
  58.0%
40
  58.0%
Systemic
22
  31.9%
22
  31.9%
Part 2 Number Analyzed 0 participants 26 participants 25 participants 51 participants
Pauciarticular
1
   3.8%
2
   8.0%
3
   5.9%
Polyarticular
17
  65.4%
14
  56.0%
31
  60.8%
Systemic
8
  30.8%
9
  36.0%
17
  33.3%
[1]
Measure Description:

Onset type is determined by manifestations during the first 6 months of disease.

Pauciarticular JRA: Arthritis in 4 or fewer joints during the first 6 months of disease.

Polyarticular JRA: Arthritis in 5 or more joints during the first 6 months of disease.

Systemic onset JRA: Arthritis with persistent intermittent fever with or without rheumatoid rash or other organ involvement.

[2]
Measure Analysis Population Description: Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.
1.Primary Outcome
Title Percentage of Participants With Disease Flare in Part 2
Hide Description

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).
Time Frame End of part 1 (day 90) and months 4 to 7
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Hide Arm/Group Description:
In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.
In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: percentage of participants
81 28
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo, Part 2: Etanercept 0.4 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0030
Comments [Not Specified]
Method Mantel Haenszel
Comments Stratified by study center and the number of active joints at randomization
2.Secondary Outcome
Title Time to Flare in Part 2
Hide Description The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.
Time Frame Months 4 to 7
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Hide Arm/Group Description:
In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.
In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Overall Number of Participants Analyzed 26 25
Median (Full Range)
Unit of Measure: days
28.0
(6 to 123)
116.0
(28 to 127)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo, Part 2: Etanercept 0.4 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug
Arm/Group Title Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Hide Arm/Group Description:
Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.
In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.
In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
Overall Number of Participants Analyzed 69 26 25
Measure Type: Count of Participants
Unit of Measure: Participants
Noninfectious adverse events
51
  73.9%
9
  34.6%
13
  52.0%
Injection site reactions
27
  39.1%
1
   3.8%
1
   4.0%
Infections
43
  62.3%
8
  30.8%
15
  60.0%
Serious adverse events
1
   1.4%
0
   0.0%
1
   4.0%
Deaths
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame 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).
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 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Hide Arm/Group Description Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. n Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months. In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.
All-Cause Mortality
Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/69 (1.45%)   0/26 (0.00%)   1/25 (4.00%) 
Infections and infestations       
Gastroenteritis  1  1/69 (1.45%)  0/26 (0.00%)  0/25 (0.00%) 
Psychiatric disorders       
Abnormal behaviour  1  0/69 (0.00%)  0/26 (0.00%)  1/25 (4.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Etanercept 0.4 mg/kg Part 2: Placebo Part 2: Etanercept 0.4 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   59/69 (85.51%)   12/26 (46.15%)   19/25 (76.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  7/69 (10.14%)  1/26 (3.85%)  1/25 (4.00%) 
Diarrhoea  1  4/69 (5.80%)  0/26 (0.00%)  2/25 (8.00%) 
Nausea  1  7/69 (10.14%)  0/26 (0.00%)  2/25 (8.00%) 
Vomiting  1  10/69 (14.49%)  0/26 (0.00%)  3/25 (12.00%) 
General disorders       
Fatigue  1  4/69 (5.80%)  1/26 (3.85%)  1/25 (4.00%) 
Injection site erythema  1  23/69 (33.33%)  1/26 (3.85%)  0/25 (0.00%) 
Injection site pain  1  10/69 (14.49%)  1/26 (3.85%)  0/25 (0.00%) 
Injection site pruritus  1  13/69 (18.84%)  1/26 (3.85%)  0/25 (0.00%) 
Injection site swelling  1  13/69 (18.84%)  1/26 (3.85%)  1/25 (4.00%) 
Pyrexia  1  2/69 (2.90%)  0/26 (0.00%)  2/25 (8.00%) 
Infections and infestations       
Ear infection  1  6/69 (8.70%)  2/26 (7.69%)  1/25 (4.00%) 
Gastroenteritis  1  5/69 (7.25%)  1/26 (3.85%)  3/25 (12.00%) 
Influenza  1  2/69 (2.90%)  2/26 (7.69%)  2/25 (8.00%) 
Pharyngitis  1  10/69 (14.49%)  0/26 (0.00%)  3/25 (12.00%) 
Tinea pedis  1  0/69 (0.00%)  0/26 (0.00%)  2/25 (8.00%) 
Upper respiratory tract infection  1  24/69 (34.78%)  4/26 (15.38%)  10/25 (40.00%) 
Nervous system disorders       
Headache  1  14/69 (20.29%)  3/26 (11.54%)  5/25 (20.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  4/69 (5.80%)  1/26 (3.85%)  1/25 (4.00%) 
Nasal congestion  1  8/69 (11.59%)  1/26 (3.85%)  2/25 (8.00%) 
Oropharyngeal pain  1  4/69 (5.80%)  0/26 (0.00%)  2/25 (8.00%) 
Rhinorrhoea  1  4/69 (5.80%)  0/26 (0.00%)  3/25 (12.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  5/69 (7.25%)  2/26 (7.69%)  0/25 (0.00%) 
Vasculitic rash  1  0/69 (0.00%)  2/26 (7.69%)  1/25 (4.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03780959     History of Changes
Other Study ID Numbers: 20021616
016.0016 ( Other Identifier: Immunex Corporation )
First Submitted: December 18, 2018
First Posted: December 19, 2018
Results First Submitted: June 10, 2019
Results First Posted: August 2, 2019
Last Update Posted: August 2, 2019