Back to resultsSafety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)
Primary Purpose
Juvenile Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Etanercept
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Juvenile Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of JRA by the American College of Rheumatology (ACR) criteria.
- Disease course must be polyarticular with disease duration long enough to have been given an adequate trial of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose methotrexate at a dose of at least 10 mg/m²/week
- Continuing active disease, defined as ≥ 5 swollen joints and ≥ 3 joints with limitation of motion accompanied by pain, tenderness or warmth.
- Disease refractory to methotrexate or intolerant of methotrexate.
- Have not received disease-modifying anti-rheumatic drugs (DMARDs) within 28 days prior to enrollment.
- Have not received methotrexate within 14 days prior to dosing of study drug.
Exclusion Criteria:
- Pregnant or nursing female
- Functional class IV by ACR criteria
- Unable to meet concomitant medication restrictions
- Intraarticular corticosteroid injection within 4 weeks prior to enrollment
Clinically significant deviations from normal, defined as:
- thrombocytopenia; platelet count < 100,000/cmm
- leukopenia; total white cell count < 4000 cells/cmm
- neutropenia; neutrophils < 1000 cells/cmm
- hepatic transaminase levels > two times the upper limit of normal (ULN)
- serum bilirubin > 2 times ULN
- creatinine clearance < 90 mL/min/1.73 m² body surface area (BSA) and/or a glomerular filtration rate (GFR) < 90 mL/min/1.73 m² BSA.
- known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity, or hepatitis C positivity.
- anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies or anti-cardiolipin antibodies present.
- Previously received antibody to TNF, antibody to cluster of differentiation (CD)4, or diphtheria interleukin (IL)-2-fusion protein (DAB-IL-2)
- Participated in a study of an investigational drug or biologic requiring informed consent within 3 months prior to study entry.
- Any concurrent medical condition which would, in the investigator's opinion, compromise the patient's ability to tolerate the study drug or make the patient unable to cooperate with the protocol.
- History of or current psychiatric illness that would interfere with ability to comply with protocol requirements or informed consent.
- History or drug or alcohol abuse that would interfere with ability to comply with protocol requirements
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Etanercept/Placebo
Etanercept/Etanercept
Arm 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.
Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to continue receiving etanercept twice weekly for up to 4 additional months.
Outcomes
Primary Outcome Measures
Percentage of Participants With Disease Flare in Part 2
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).
Secondary Outcome Measures
Time to Flare in Part 2
The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.
Number of Participants With Adverse Events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03780959
Brief Title
Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)
Official Title
Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
May 1, 1997 (Actual)
Primary Completion Date
July 8, 1998 (Actual)
Study Completion Date
July 8, 1998 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study was to determine the efficacy of etanercept in children with polyarticular course JRA.
Detailed Description
This was a two-part study. In the first part of the study, all participants received open-label etanercept twice a week for 90 days. At the end of the 90 days, participants with disease response as defined by the JRA Definition of Improvement (DOI) using the JRA Core Set Criteria were randomized in part 2 of the study to receive placebo or continued administration of etanercept until either disease flare occurred or 4 months elapsed, whichever was earlier.
Participants who did not meet the DOI at day 90, participants who had disease flare during part 2 and participants who completed the blinded part of the study were eligible to receive open-label treatment with etanercept under protocol 16.0018 (NCT00357903).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Etanercept/Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Etanercept/Etanercept
Arm Type
Experimental
Arm Description
Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to continue receiving etanercept twice weekly for up to 4 additional months.
Intervention Type
Drug
Intervention Name(s)
Etanercept
Other Intervention Name(s)
Enbrel, TNFR:Fc
Intervention Description
Administered twice weekly by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered twice weekly by subcutaneous injection
Primary Outcome Measure Information:
Title
Percentage of Participants With Disease Flare in Part 2
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
Secondary Outcome Measure Information:
Title
Time to Flare in Part 2
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
Title
Number of Participants With Adverse Events
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of JRA by the American College of Rheumatology (ACR) criteria.
Disease course must be polyarticular with disease duration long enough to have been given an adequate trial of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose methotrexate at a dose of at least 10 mg/m²/week
Continuing active disease, defined as ≥ 5 swollen joints and ≥ 3 joints with limitation of motion accompanied by pain, tenderness or warmth.
Disease refractory to methotrexate or intolerant of methotrexate.
Have not received disease-modifying anti-rheumatic drugs (DMARDs) within 28 days prior to enrollment.
Have not received methotrexate within 14 days prior to dosing of study drug.
Exclusion Criteria:
Pregnant or nursing female
Functional class IV by ACR criteria
Unable to meet concomitant medication restrictions
Intraarticular corticosteroid injection within 4 weeks prior to enrollment
Clinically significant deviations from normal, defined as:
thrombocytopenia; platelet count < 100,000/cmm
leukopenia; total white cell count < 4000 cells/cmm
neutropenia; neutrophils < 1000 cells/cmm
hepatic transaminase levels > two times the upper limit of normal (ULN)
serum bilirubin > 2 times ULN
creatinine clearance < 90 mL/min/1.73 m² body surface area (BSA) and/or a glomerular filtration rate (GFR) < 90 mL/min/1.73 m² BSA.
known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity, or hepatitis C positivity.
anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies or anti-cardiolipin antibodies present.
Previously received antibody to TNF, antibody to cluster of differentiation (CD)4, or diphtheria interleukin (IL)-2-fusion protein (DAB-IL-2)
Participated in a study of an investigational drug or biologic requiring informed consent within 3 months prior to study entry.
Any concurrent medical condition which would, in the investigator's opinion, compromise the patient's ability to tolerate the study drug or make the patient unable to cooperate with the protocol.
History of or current psychiatric illness that would interfere with ability to comply with protocol requirements or informed consent.
History or drug or alcohol abuse that would interfere with ability to comply with protocol requirements
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)
We'll reach out to this number within 24 hrs