Juvenile Rheumatoid ArthritisPhase 3NCT03781375
Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
A Phase 3 study testing Etanercept and Methotrexate in people with Juvenile Rheumatoid Arthritis, run by Amgen.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Juvenile Rheumatoid Arthritis
- What is being tested?
- Etanercept and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 24 Aug 2000to 24 Jun 2002
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
- Any concurrent medical condition which would have, in the investigator's opinion, compromised the patient's ability to tolerate the study drug or would have made the patient unable to cooperate with the protocol
- History of/or current psychiatric illness that would have interfered with ability to comply with protocol requirements or give informed consent
- Chronic or recurrent infections, or currently active infection at screening
- History of alcohol or drug abuse that would have interfered with ability to comply with protocol requirements
- Inability to have complied with the study requirements
About this study
Official title: A Phase III Double Blind Randomized Study Comparing Etanercept (Enbrel) Combined With Methotrexate vs Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
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
- Being tested
- Etanercept, Placebo to Etanerceot, Methotrexate
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Also called Enbrel
Administered by subcutaneous injection twice a week
Placebo to EtanerceotDrug
Administered by subcutaneous injection twice a week
MethotrexateDrug
Administered orally or subcutaneously once a week at the same dose as prior to study entry
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Etanercept; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline and month 6
Secondary outcomes (2)
Percentage of Participants With a 50% Improvement in JRA DOI at Month 6
Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 50% 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)
Measured: Baseline and month 6
Percentage of Participants With a 70% Improvement in JRA DOI at Month 6
Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 70% 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)
Measured: Baseline and month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start24 Aug 2000
- Primary completion20 Jun 2002
- Study completion24 Jun 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Juvenile Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03781375
- Sponsor's protocol ID
- 20021628
- Other IDs
- 016.0028
- Status last verified
- Jun 2019
- First submitted
- 18 Dec 2018
- Last updated
- 2 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Double Blind Randomized Study Comparing Etanercept (Enbrel) Combined With Methotrexate vs Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03781375
- Acronym / sponsor ID
- 20021628
- Conditions
- Juvenile Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 25 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2000 (actual)
- Primary completion
- 20 Jun 2002 (actual)
- Study completion
- 24 Jun 2002 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Posted 2 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate + Placebo | Placebo comparator | Drug: Etanercept, Drug: Placebo to Etanerceot, Drug: MethotrexateParticipants 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. |
| Methotrexate + Etanercept | Experimental | Drug: Etanercept, Drug: MethotrexateParticipants 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. |
Who may qualify
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (20 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtanerceptAlso: EnbrelAdministered by subcutaneous injection twice a week | Drug | Methotrexate + Etanercept, Methotrexate + Placebo |
| Placebo to EtanerceotAdministered by subcutaneous injection twice a week | Drug | Methotrexate + Placebo |
| MethotrexateAdministered orally or subcutaneously once a week at the same dose as prior to study entry | Drug | Methotrexate + Etanercept, Methotrexate + Placebo |
Primary outcome
Percentage of Participants With a JRA Response at Month 6
Time frame: Baseline and 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)
2 secondary outcomes
Percentage of Participants With a 50% Improvement in JRA DOI at Month 6
Time frame: Baseline and month 6
Percentage of Participants With a 70% Improvement in JRA DOI at Month 6
Time frame: Baseline and month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etanercept and Methotrexate in people with Juvenile Rheumatoid Arthritis, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With a JRA Response at Month 6 (time frame: Baseline and month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2019.