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

NCT03781375 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: 20021628016.0028
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study was to determine the efficacy of etanercept plus methotrexate vs methotrexate alone in pediatric patients with active polyarticular course juvenile rheumatoid arthritis (JRA).

Conditions

Juvenile Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a JRA Response at Month 6

  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)

  Baseline and month 6

Secondary Outcomes (2)

• Percentage of Participants With a 50% Improvement in JRA DOI at Month 6

  Baseline and month 6

• Percentage of Participants With a 70% Improvement in JRA DOI at Month 6

  Baseline and month 6

Study Arms (2)

Methotrexate + Placebo

PLACEBO COMPARATOR

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.

Drug: Etanercept; Drug: Placebo to Etanerceot; Drug: Methotrexate

Methotrexate + Etanercept

EXPERIMENTAL

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.

Drug: Etanercept; Drug: Methotrexate

Interventions

Etanercept DRUG

Administered by subcutaneous injection twice a week

Also known as: Enbrel

Methotrexate + Etanercept; Methotrexate + Placebo

Placebo to Etanerceot DRUG

Administered by subcutaneous injection twice a week

Methotrexate + Placebo

Methotrexate DRUG

Administered orally or subcutaneously once a week at the same dose as prior to study entry

Methotrexate + Etanercept; Methotrexate + Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have had a diagnosis of JRA by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular
• Disease course must have been polyarticular with at least 5 active joints
• Duration of disease was not limited, but must have been long enough for the patient to have been given a 3-month trial of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate at a dose between 0.3 and 1.0 mg/kg/week, orally (PO) or subcutaneously (SC)
• Receiving methotrexate at a dose between 0.3 mg/kg/wk and 1 mg/kg/wk at time of randomization. The dose of methotrexate must have been stable for one month prior to entry
• Patients may have failed prednisone, or been on a dosage of prednisone not to have exceeded 10 mg/day or 0.20 mg/kg/day (whichever was less)
• At the time of qualification (screening) for study and prior to wash-out of all disease modifying anti-rheumatic drugs (DMARDs), the patient must have had active disease, defined as ≥ 5 swollen joints accompanied by pain, and/or tenderness and/or warmth, and ≥ 3 joints with limitation of motion (LOM). (The joints with LOM may have been the same as those with swelling)
• Had good venous access and stable hematocrit ≥ 24 mL/dL
• Patients must have been pre-pubescent, or if post-pubertal at anytime during the study, and of child-bearing potential, must have been practicing adequate contraception
• Parent or legal guardian was able and willing to give informed consent
• Parent or legal guardian must have been willing to actively supervise storage and administration of study drug and ensure that the date and time of each dose was accurately recorded in the subject's diary

You may not qualify if:

• Was unable to meet the concurrent medication restrictions as described in the protocol
• Pregnant or nursing female
• Patients were excluded if they demonstrated clinically significant deviations from normal (as defined below) in any of the following laboratory parameters:
• 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 \> two times the ULN
• estimated creatinine clearance of \< 90 mL/min/1.73 M² body surface area (BSA)
• known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity not related to vaccination, or hepatitis C antibody positivity
• Had received etanercept, antibody to tumor necrosis factor (TNF) (i.e. infliximab or D2E7), antibody to cluster of differentiation (CD)4 (anti-CD4), diphtheria interleukin (IL)-2 fusion protein (DAB-IL-2) or leflunomide
• Had received DMARDs including D-penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold, cyclosporin, azathioprine; intravenous immunoglobulin (IV Ig); or broadly immunosuppressant chemotherapeutic agents (e.g. cyclophosphamide, FK506, mycophenolate mofetil \[CellCept\]), for at least 28 days prior to enrollment and dosing of study drug. All DMARDs, other than methotrexate, must have been washed-out for a minimum of 28 days
• Had received intraarticular glucocorticoid injection within 28 days prior to enrollment on study
• Had previously received live virus vaccine within 3 months prior to study entry
• Had participated in a study of an investigational drug or biologic requiring informed-consent within three months prior to study entry

Sponsors & Collaborators

• Amgen: lead

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Etanercept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 19, 2018
• Study Start: August 24, 2000
• Primary Completion: June 20, 2002
• Study Completion: June 24, 2002
• Last Updated: August 2, 2019
• Results First Posted: August 2, 2019

Record last verified: 2019-06