Juvenile Rheumatoid ArthritisPhase 2/3NCT03780959
Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)
A Phase 2/3 study testing Etanercept in people with Juvenile Rheumatoid Arthritis, run by Amgen.
Trial summary
The primary objective of this study was to determine the efficacy of etanercept in children with polyarticular course JRA. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Juvenile Rheumatoid Arthritis
- What is being tested?
- Etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- No sites listed yet
- Study dates
- 1 May 1997to 8 Jul 1998
- Phase
- Phase 2/3
- 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 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
About this study
Official title: Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis
The primary objective of this study was to determine the efficacy of etanercept in children with polyarticular course JRA.
Read the 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).
- Conditions
- Juvenile Rheumatoid Arthritis
- Being tested
- Etanercept, Placebo
- 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, TNFR:Fc
Administered twice weekly by subcutaneous injection
PlaceboDrug
Administered twice weekly by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Etanercept/Placebo | Placebo comparator | 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. Receives: Drug: Etanercept; Drug: Placebo |
| Etanercept/Etanercept | Experimental | 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. Receives: Drug: Etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: End of part 1 (day 90) and months 4 to 7
Secondary outcomes (2)
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.
Measured: Months 4 to 7
Number of Participants With Adverse Events
Measured: 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).
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 start1 May 1997
- Primary completion8 Jul 1998
- Study completion8 Jul 1998
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03780959
- Sponsor's protocol ID
- 20021616
- Other IDs
- 016.0016
- 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
- Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03780959
- Acronym / sponsor ID
- 20021616
- Conditions
- Juvenile Rheumatoid Arthritis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 May 1997 (actual)
- Primary completion
- 8 Jul 1998 (actual)
- Study completion
- 8 Jul 1998 (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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etanercept/Placebo | Placebo comparator | Drug: Etanercept, Drug: PlaceboParticipants 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. |
| Etanercept/Etanercept | Experimental | Drug: EtanerceptParticipants 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. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
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: Enbrel, TNFR:FcAdministered twice weekly by subcutaneous injection | Drug | Etanercept/Etanercept, Etanercept/Placebo |
| PlaceboAdministered twice weekly by subcutaneous injection | Drug | Etanercept/Placebo |
Primary outcome
Percentage of Participants With Disease Flare in Part 2
Time frame: End of part 1 (day 90) and months 4 to 7
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).
2 secondary outcomes
Time to Flare in Part 2
Time frame: Months 4 to 7
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).
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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Etanercept 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 6 inclusion and 18 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: finished, 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Disease Flare in Part 2 (time frame: End of part 1 (day 90) and months 4 to 7). 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.