Clinical trial NCT03780959: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Juvenile Rheumatoid Arthritis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-12-19
Enrollment: 69
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Percentage of Participants With Disease Flare in Part 2
timeFrame: End of part 1 (day 90) and months 4 to 7
Secondary outcomes:
measure: Time to Flare in Part 2
timeFrame: Months 4 to 7
measure: Number of Participants With Adverse Events
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).
Other outcomes:
Locations:
Study officials:
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