Rheumatoid ArthritisPhase 4EMPIRENCT01303874
Etanercept and Methotrexate in Patients to Induce Remission in Early Arthritis (EMPIRE)
A Phase 4 study testing Etanercept (ETN) in people with Rheumatoid Arthritis and Inflammatory Arthritis, run by University of Leeds at 1 site in United Kingdom.
Trial summary
TRIAL DESIGN 1. Description This is a 18-month, double-blind, randomized, multicentre, outpatient study. The approximate duration of subject participation will be 18 months and the approximate total duration of the study will be 42 months. The duration of subject enrollment will be approximately 24 months. 2. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis, Inflammatory Arthritis
- What is being tested?
- Etanercept (ETN)
- 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
- 112 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2006to 5 Nov 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is age 18 -80 years old
- Patients have articular synovitis, within 3 months of diagnosis
- Either RF antibody (+) or anti-CCP antibody (+) or SE (+)
- Demonstrates a negative urine pregnancy test at screening if female of childbearing potential
- Agrees to use a medically accepted form of contraception during the study and for 3 months after the last dose of study drug, if sexually active male
- Is capable of understanding and signing an informed consent form
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- Is able and willing to self-inject study drug or have a designee who can do so
- Is able and willing to take oral medication
- Is able to store injectable test article at 2° C to 8° C
- Demonstrates a negative tuberculosis screening test
Who cannot join
- Received previous treatment with any DMARDS
- Received previous treatment with ETN or other tumour necrosis factor (TNF) antagonist (e.g. a TNF monoclonal antibody or a soluble TNF-receptor)
- Previous treatment with IL-1 receptor antagonist
- Chronic arthritis diagnosed before 16 years old
- Received any investigational "biological" agent within 3 months of screening visit
- Received treatment with any investigational drug of "chemical" nature within one month prior to study screening
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- Known Human Immunodeficiency Virus (HIV)
- Presence of any contraindication to ETN or MTX
- Has significant concurrent medical diseases
- Has cancer or a history of cancer within 5 years of entering the screening period
- Current crystal or infective arthritis
- Chronic infection of the upper respiratory tract, chest, urinary tract or skin
- Any ongoing or active infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days
- Demonstrates liver function abnormality
- Has renal disease
- Has leukopenia
- Has thrombocytopenia
- Has a hemoglobin level of < 9g/L for males and < 85 g/L for females
- Is pregnant or breast-feeding
- Joint surgery within preceding 2 months (at joints to be assessed within this study)
- Received anti-CD4, diphtheria interleukin-2 fusion protein, anti-interleukin-6 (anti-IL-6), rituximab or other immunosuppressive biologic during the last 6 months before screening, and treatment with such agents more than 6 months before screening if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening visit
- Received any live (attenuated) vaccines within 4 weeks of screening visit
- Received cyclophosphamide within 6 months of screening visit
- Any corticosteroids within 28days prior to screening
- Uses a dose of NSAID greater than the maximum recommended dose in the product information at the screening visit
- Has a history of confirmed blood dyscrasia
- Has any condition judged by the physician to cause this study to be detrimental to the subject
- Has a history of drug abuse or psychiatric disease that would interfere with the ability to comply with the study protocol
- Has a history of alcohol abuse or excessive alcohol beverage consumption
- Has a history of known liver cirrhosis, fibrosis, or fatty liver
- Has a history of any viral hepatitis within 1 year of screening
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leeds Teaching Hospital HNS Trust
Leeds, West Yorkshire, LS7 4SA
About this study
Official title: A Multicentre Randomised Trial Of Etanercept And Methotrexate To Induce Remission In Early Inflammatory Arthritis
TRIAL DESIGN
- Description This is a 18-month, double-blind, randomized, multicentre, outpatient study. The approximate duration of subject participation will be 18 months and the approximate total duration of the study will be 42 months. The duration of subject enrollment will be approximately 24 months.
- Discussion of Trial Design The study is designed to directly compare the effectiveness of combination therapy with MTX + ETN versus
- Principal research question/objective To determine the number of patients in clinical remission at 12 months of follow-up, as defined as the absence of symptoms and signs of inflammatory arthritis.
Read the detailed description
Early arthritis is frequently undifferentiated. It is well recognised that a substantial proportion of patients with an undifferentiated inflammatory arthritis will go on to develop persistent synovitis, with the strongest predictor of persistence being disease duration > 12 weeks (1-4). Studies have shown that patients with early oligoarthritis who fail to respond within 2 weeks to corticosteroid injections have a high likelihood of persistent disease (2). It is therefore clear that these patients with early inflammatory arthritis need definitive treatment, but the optimal therapeutic strategy is yet to be determined.
Tumor Necrosis Factor (TNF) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory process of rheumatoid and other arthritis, and the resulting joint pathology. Elevated levels of TNF are found in the synovial fluid of patients with RA. Two distinct receptors for TNF exist naturally as monomeric molecules on the cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNF receptors (TNFR). Etanercept (ETN) is a dimeric fusion protein consisting of the p75 TNFR linked to the Fc portion of human IgG1, and is capable of binding two TNF molecules. Etanercept inhibits binding of both TNF-alpha and TNF-beta to cell surface TNFRs, rendering TNF biologically inactive. Agents that block TNF are effective in all types of arthritis (with the exclusion of connective tissue diseases).
It is generally agreed that there is a window of opportunity in active early inflammatory arthritis in which definitive treatment may give a disproportionate improvement compared to treatment at a later time, and may well be able to induce remission in a subgroup of patients.
Studies in early rheumatoid arthritis (< 12 months) have shown that remission-induction with the TNF-antagonist infliximab provides a significant reduction in MRI-evidence of synovitis and erosions at 12 months with evidence of sustained functional and quality of life benefits at 2 years, despite withdrawal of infliximab at 12 months (5). Results from the TEMPO study show that treatment of established rheumatoid arthritis with ETN+MTX achieves remission in about 40% patients (6). TNF antagonists also have the therapeutic benefit of rapid and sustained suppression of inflammation.
Treatment of patients with early undifferentiated arthritis with ETN+MTX is hypothesised to prevent progression of persistent disabling disease in a significant number of patients. Induction of remission at this time in the disease course may result in sustained remission, reduce the need for further treatment, and be most cost effective therapeutic strategy.
- Conditions
- Rheumatoid Arthritis, Inflammatory Arthritis
- Being tested
- Etanercept (ETN), Placebo
- Keywords
- Rheumatoid arthritis, Inflammatory arthritis, Undifferentiated arthritis, Etanercept, Combination Therapy
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etanercept (ETN)Drug
Also called Enbrel
ETN 50 mg subcutaneous (SC) injections once weekly and MTX orally once weekly.
PlaceboDrug
Also called Maxtrex
ETN-matching placebo SC injections once weekly and MTX orally once weekly.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Methotrexate \& Etanercept Receives: Drug: Etanercept (ETN) |
| Single-agent therapy | Placebo comparator | Methotrexate (MTX) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical remission
To determine the number of patients in clinical remission at 12 months, as defined as the absence of symptoms and signs of inflammatory arthritis (i.e. swollen joint count 0; tender joint count 0)
Measured: 12 months
Secondary outcomes (9)
clinical remission
The number of patients in clinical remission at 18 months (as defined as absence of symptoms and signs of clinical arthritis i.e. swollen joint count 0 ; tender joint count 0)
Measured: 18 months
Conventional disease activity measures
Conventional disease activity measures (VAS pain/fatigue/global/physician, EMS, TJC, SJC, CRP, ESR)
Measured: week 78
Functional, work and quality of life assessments
Functional, work and quality of life assessments (HAQ, WIS, WDA, EQ-5d, SF-36)
Measured: Week 78
remission
Proportion of patients achieving 26 weeks of remission
Measured: Week 26
DAS 44
Disease Activity Score (DAS) 44
Measured: Week 78
drug-free remission
The number of patients in drug-free remission at 12 18 months
Measured: 12 & 18 mths
etanercept-free remission
The number of patients in etanercept-free remission at 12 and 18 months (ETN arm)
Measured: 12 and 18 months
Remission by ACR Criteria
Remission by ACR Criteria
Measured: Week 78
effects of the combination of ETN and MTX to MTX alone on radiographic change
To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change at 12 months and 18 months
Measured: 12 months and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2011 (estimated)
- Study startSep 2006
- Primary completion5 Nov 2010
- Study completion5 Nov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Emery, University of Leeds
- Investigators
- Paul Emery, Prof, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01303874
- Sponsor's protocol ID
- RR05/7150
- Other IDs
- 2005-005467-29, 2005
- Acronym
- EMPIRE
- Status last verified
- Oct 2019
- First submitted
- 24 Feb 2011
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Randomised Trial Of Etanercept And Methotrexate To Induce Remission In Early Inflammatory Arthritis
- ClinicalTrials.gov ID
- NCT01303874
- Acronym / sponsor ID
- EMPIRE / RR05/7150
- Conditions
- Rheumatoid Arthritis, Inflammatory Arthritis
- Keywords
- Rheumatoid arthritis, Inflammatory arthritis, Undifferentiated arthritis, Etanercept, Combination Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- 5 Nov 2010 (actual)
- Study completion
- 5 Nov 2010 (actual)
- First posted
- 25 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TRIAL DESIGN
- Description This is a 18-month, double-blind, randomized, multicentre, outpatient study. The approximate duration of subject participation will be 18 months and the approximate total duration of the study will be 42 months. The duration of subject enrollment will be approximately 24 months.
- Discussion of Trial Design The study is designed to directly compare the effectiveness of combination therapy with MTX + ETN versus
- Principal research question/objective To determine the number of patients in clinical remission at 12 months of follow-up, as defined as the absence of symptoms and signs of inflammatory arthritis.
Detailed description
Early arthritis is frequently undifferentiated. It is well recognised that a substantial proportion of patients with an undifferentiated inflammatory arthritis will go on to develop persistent synovitis, with the strongest predictor of persistence being disease duration > 12 weeks (1-4). Studies have shown that patients with early oligoarthritis who fail to respond within 2 weeks to corticosteroid injections have a high likelihood of persistent disease (2). It is therefore clear that these patients with early inflammatory arthritis need definitive treatment, but the optimal therapeutic strategy is yet to be determined.
Tumor Necrosis Factor (TNF) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory process of rheumatoid and other arthritis, and the resulting joint pathology. Elevated levels of TNF are found in the synovial fluid of patients with RA. Two distinct receptors for TNF exist naturally as monomeric molecules on the cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNF receptors (TNFR). Etanercept (ETN) is a dimeric fusion protein consisting of the p75 TNFR linked to the Fc portion of human IgG1, and is capable of binding two TNF molecules. Etanercept inhibits binding of both TNF-alpha and TNF-beta to cell surface TNFRs, rendering TNF biologically inactive. Agents that block TNF are effective in all types of arthritis (with the exclusion of connective tissue diseases).
It is generally agreed that there is a window of opportunity in active early inflammatory arthritis in which definitive treatment may give a disproportionate improvement compared to treatment at a later time, and may well be able to induce remission in a subgroup of patients.
Studies in early rheumatoid arthritis (< 12 months) have shown that remission-induction with the TNF-antagonist infliximab provides a significant reduction in MRI-evidence of synovitis and erosions at 12 months with evidence of sustained functional and quality of life benefits at 2 years, despite withdrawal of infliximab at 12 months (5). Results from the TEMPO study show that treatment of established rheumatoid arthritis with ETN+MTX achieves remission in about 40% patients (6). TNF antagonists also have the therapeutic benefit of rapid and sustained suppression of inflammation.
Treatment of patients with early undifferentiated arthritis with ETN+MTX is hypothesised to prevent progression of persistent disabling disease in a significant number of patients. Induction of remission at this time in the disease course may result in sustained remission, reduce the need for further treatment, and be most cost effective therapeutic strategy.
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 |
|---|---|---|
| Combination Therapy | Experimental | Drug: Etanercept (ETN)Methotrexate \& Etanercept |
| Single-agent therapy | Placebo comparator | Drug: PlaceboMethotrexate (MTX) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Is age 18 -80 years old
- Patients have articular synovitis, within 3 months of diagnosis
- Either RF antibody (+) or anti-CCP antibody (+) or SE (+)
- Demonstrates a negative urine pregnancy test at screening if female of childbearing potential
- Agrees to use a medically accepted form of contraception during the study and for 3 months after the last dose of study drug, if sexually active male
Key exclusion criteria (31 listed)
- Received previous treatment with any DMARDS
- Received previous treatment with ETN or other tumour necrosis factor (TNF) antagonist (e.g. a TNF monoclonal antibody or a soluble TNF-receptor)
- Previous treatment with IL-1 receptor antagonist
- Chronic arthritis diagnosed before 16 years old
- Received any investigational "biological" agent within 3 months of screening visit
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 |
|---|---|---|
| Etanercept (ETN)Also: EnbrelETN 50 mg subcutaneous (SC) injections once weekly and MTX orally once weekly. | Drug | Combination Therapy |
| PlaceboAlso: MaxtrexETN-matching placebo SC injections once weekly and MTX orally once weekly. | Drug | Single-agent therapy |
Primary outcome
clinical remission
Time frame: 12 months
To determine the number of patients in clinical remission at 12 months, as defined as the absence of symptoms and signs of inflammatory arthritis (i.e. swollen joint count 0; tender joint count 0)
9 secondary outcomes
clinical remission
Time frame: 18 months
Conventional disease activity measures
Time frame: week 78
Functional, work and quality of life assessments
Time frame: Week 78
remission
Time frame: Week 26
DAS 44
Time frame: Week 78
drug-free remission
Time frame: 12 & 18 mths
etanercept-free remission
Time frame: 12 and 18 months
Remission by ACR Criteria
Time frame: Week 78
effects of the combination of ETN and MTX to MTX alone on radiographic change
Time frame: 12 months and 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
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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.
Paul Emery, Prof principal investigator
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Etanercept (ETN) in people with Rheumatoid Arthritis and Inflammatory Arthritis, run by University of Leeds at 1 site in United Kingdom.
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 31 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 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
clinical remission (time frame: 12 months). 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 1 Nov 2019.