Rheumatoid ArthritisPhase 4JESMRNCT00688103
Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan
A Phase 4 study testing ETN Alone and ETN+MTX in people with Rheumatoid Arthritis, run by Japan Biological Agent Study Integrated Consortium at 1 site in Japan.
Trial summary
Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups. 1. Etanercept alone treatment group (25mg, twice/week, s.c.) 2. Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- ETN Alone and ETN+MTX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 1 siteJapan
- Study dates
- Jun 2005to Oct 2010
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients had to be at least 18 years of age
- fulfilled the 1987 revised classification criteria for RA by in American College of Rheumatology (ACR)
- met the guidelines for the proper use of ETN in Japan (having at least 6 tender joints and 6 swollen joints
- either serum C-reactive protein more than 2 mg/dl or ESR no less than 28 mm at 1 hour, with adequate safety profiles)
- be ACR functional class I-III
- have been receiving MTX 6 mg/week for a minimum of 3 months at a stable dose for at least 4 weeks at the time of study enrollment
Who cannot join
- Patients who required concurrent use of prednisone (PSL) >10 mg/day, or its equivalent, were excluded from study entry
- the start of dose increment of PSL equivalents within 3 months of the study enrollment
- experience of antirheumatic therapy except for MTX and PSL equivalents
- previous treatment with ETN or any other biological treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Etanercept in Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan
Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups.
- Etanercept alone treatment group (25mg, twice/week, s.c.)
- Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
- Conditions
- Rheumatoid Arthritis
- Being tested
- ETN Alone, ETN+MTX
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ETN AloneDrug
Also called etanercept
etanercept (25 mg, twice/week, s.c.)
ETN+MTXDrug
Also called etanercept and methotrexate
etanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week)
| Study group | Role | What they receive |
|---|---|---|
| ETN Alone | Active comparator | etanercept (25mg, twice/week, s.c.) Receives: Drug: ETN Alone |
| ETN+MTX | Active comparator | etanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week) Receives: Drug: ETN+MTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
EULAR Good Response
EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by > 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 < 3.2 is regarded as low disease activity.
Measured: at 24 weeks
ACR50 Response Rate
ACR (American College of Rheumatology) 50 response is defined by the following definition of improvement: at least 50% improvement in tender and swollen joint counts and at least 50% improvement in 3 of the 5 remaining ACR-core set measures; patient and physician global assessments, pain, disability, and an acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).
Measured: at 24 weeks
Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score
The van der Heijde-modifiedtotal Sharp score is the sum of scores for erosions and joint space narrowing. The minimum and maximum total scores are 0 and 448, respectively. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively.
Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet.
For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Measured: at 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2008 (estimated)
- Study startJun 2005
- Primary completionOct 2008
- Study completionOct 2010
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.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Japan Biological Agent Study Integrated Consortium
- Sponsor type
- Research network
- Responsible party
- Principal investigator, Hideto Kameda, Japan Biological Agent Study Integrated Consortium
- Investigators
- Tsutomu Takeuchi, MD, PhD, Study chair, JBASIC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00688103
- Sponsor's protocol ID
- Etanercept-01
- Acronym
- JESMR
- Status last verified
- Sep 2015
- First submitted
- 25 May 2008
- Last updated
- 1 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kameda H, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Takeuchi T; Japan Biological Agent Study Integrated Consortium. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol. 2010 Dec;20(6):531-8. doi: 10.1007/s10165-010-0324-4. Epub 2010 Jun 24.
PubMed 20574649Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T. Continuation of methotrexate resulted in better clinical and radiographic outcomes than discontinuation upon starting etanercept in patients with rheumatoid arthritis: 52-week results from the JESMR study. J Rheumatol. 2011 Aug;38(8):1585-92. doi: 10.3899/jrheum.110014. Epub 2011 May 15.
PubMed 21572151Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T; Japan Biological Agent Integrated Consortium (JBASIC). A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study. Ann Rheum Dis. 2013 Feb;72(2):310-2. doi: 10.1136/annrheumdis-2012-201804. Epub 2012 Sep 12. No abstract available.
PubMed 22975754
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Etanercept in Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan
- ClinicalTrials.gov ID
- NCT00688103
- Acronym / sponsor ID
- JESMR / Etanercept-01
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Japan Biological Agent Study Integrated ConsortiumResearch network
- Study start
- Jun 2005
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 2 Jun 2008 (estimated)
- Results
- Posted 1 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups.
- Etanercept alone treatment group (25mg, twice/week, s.c.)
- Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ETN Alone | Active comparator | Drug: ETN Aloneetanercept (25mg, twice/week, s.c.) |
| ETN+MTX | Active comparator | Drug: ETN+MTXetanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients had to be at least 18 years of age
- fulfilled the 1987 revised classification criteria for RA by in American College of Rheumatology (ACR)
- met the guidelines for the proper use of ETN in Japan (having at least 6 tender joints and 6 swollen joints
- either serum C-reactive protein more than 2 mg/dl or ESR no less than 28 mm at 1 hour, with adequate safety profiles)
- be ACR functional class I-III
Key exclusion criteria (4 listed)
- Patients who required concurrent use of prednisone (PSL) >10 mg/day, or its equivalent, were excluded from study entry
- the start of dose increment of PSL equivalents within 3 months of the study enrollment
- experience of antirheumatic therapy except for MTX and PSL equivalents
- previous treatment with ETN or any other biological treatment
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 |
|---|---|---|
| ETN AloneAlso: etanerceptetanercept (25 mg, twice/week, s.c.) | Drug | ETN Alone |
| ETN+MTXAlso: etanercept and methotrexateetanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week) | Drug | ETN+MTX |
Primary outcome
EULAR Good Response
Time frame: at 24 weeks
EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by > 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 < 3.2 is regarded as low disease activity.
ACR50 Response Rate
Time frame: at 24 weeks
ACR (American College of Rheumatology) 50 response is defined by the following definition of improvement: at least 50% improvement in tender and swollen joint counts and at least 50% improvement in 3 of the 5 remaining ACR-core set measures; patient and physician global assessments, pain, disability, and an acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).
Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score
Time frame: at 52 weeks
The van der Heijde-modifiedtotal Sharp score is the sum of scores for erosions and joint space narrowing. The minimum and maximum total scores are 0 and 448, respectively. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20574649Kameda H, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Takeuchi T; Japan Biological Agent Study Integrated Consortium. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol. 2010 Dec;20(6):531-8. doi: 10.1007/s10165-010-0324-4. Epub 2010 Jun 24.
- Results publication: PubMed 21572151Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T. Continuation of methotrexate resulted in better clinical and radiographic outcomes than discontinuation upon starting etanercept in patients with rheumatoid arthritis: 52-week results from the JESMR study. J Rheumatol. 2011 Aug;38(8):1585-92. doi: 10.3899/jrheum.110014. Epub 2011 May 15.
- Results publication: PubMed 22975754Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T; Japan Biological Agent Integrated Consortium (JBASIC). A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study. Ann Rheum Dis. 2013 Feb;72(2):310-2. doi: 10.1136/annrheumdis-2012-201804. Epub 2012 Sep 12. No abstract available.
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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.
Tsutomu Takeuchi, MD, PhD study chair
JBASIC
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 ETN Alone and ETN+MTX in people with Rheumatoid Arthritis, run by Japan Biological Agent Study Integrated Consortium at 1 site in Japan.
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 4 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 Oct 2015. 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 Japan. 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. 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?
Yes. Results are posted in the registry (first posted 1 Oct 2015). 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?
EULAR Good Response (time frame: at 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00688103, which also lists 3 linked publications.
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 Oct 2015.