Rheumatoid ArthritisPhase 4TREMERANCT04157010
Tocilizumab REMission in Early RA
A Phase 4 study testing Tocilizumab and Methotrexate in people with Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.
Trial summary
The TREMERA study focuses on patients with newly diagnosed, untreated, rheumatoid arthritis (RA). Recent international treatment recommendations emphasise the need to diagnose RA early and start treatment immediately (this being associated with better response rates); and to aim for the goal of remission i.e. 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?
- Tocilizumab and Methotrexate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2013to 29 Mar 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of rheumatoid arthritis (2010 ACR/EULAR RA classification criteria)
- Symptom duration ≤12months
- No previous disease modifying antirheumatic drug (DMARD) therapy
- Active RA at baseline (defined as: DAS28 ≥ 3.2)
- Active hand and/or wrist joint evaluable by US and MRI (with no planned surgery during the study period)
- Patients without any contraindication to MRI
Who cannot join
- Patients unwilling or unable to receive MTX for the duration of the study.
- Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosis, or any arthritis with onset prior to 16 years of age.
- Suspicion of diagnosis of tuberculosis (TB): positive quantiferon +/abnormal chest x-ray, as per clinician judgement. Prior history of TB with confirmed full chemotherapy +/latent TB adequately treated may be included as per physician's discretion.
- Intramuscular, oral or intraarticular (of non-target joint) corticosteroid within 28 days of the screening visit; intra-articular steroid of the chosen target joint within 12 weeks of screening.
- Patients with serious infections within 3 month of enrolment (screening) or persistent infections.
- Patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ).
- Known positive serology for hepatitis B or C, or HIV
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leeds Teaching Hospitals NHS Trust
Leeds, West Yorkshire, LS7 4SA
About this study
Official title: Prospective, Single-centre, Open-Label, Randomised, Pilot Study Assessing the Changes in Expression of Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) and Speed & Depth of Remission Induced by Tocilizumab & Methotrexate Combination and Tocilizumab Monotherapy in Patients With Early Rheumatoid Arthritis
The TREMERA study focuses on patients with newly diagnosed, untreated, rheumatoid arthritis (RA). Recent international treatment recommendations emphasise the need to diagnose RA early and start treatment immediately (this being associated with better response rates); and to aim for the goal of remission i.e. the absence of signs and symptoms of active inflammatory disease activity which is associated with better outcomes for the patient. Remission is more achievable with significant treatment advances that have been made in the form of highly effective biologic therapies. Tocilizumab (TCZ) is a newly introduced biologic drug that is used in established RA. The TREMERA study primarily aims to investigate the biological changes seen in blood and tissue following TCZ therapy this will contribute to a better understanding of how the drug works as well as disease processes; and will also identify whether administering a biologic drug such as TCZ can also switch off immunological parameters associated with a disrupted immune system of RA. The study will assess the effectiveness of TCZ given on its own or in combination with methotrexate (MTX; a standard therapy usually given with biologic treatments)in patients with early onset RA to determine the proportion that achieve remission. This study also aims to find out how quickly remission can be achieved with TCZ and the depth of remission achieved. This will be done using usual clinical assessment but also imaging such as ultrasound and magnetic resonance imaging (MRI) which can detect inflammation not apparent on clinical assessment.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Tocilizumab, Methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
MethotrexateDrug
| Study group | Role | What they receive |
|---|---|---|
| TCZ monotherapy | Experimental | Tocilizumab (TCZ) monotherapy 8mg/kg 4-weekly for a total of 48 weeks. Receives: Drug: Tocilizumab |
| TCZ+MTX combination therapy | Experimental | Tocilizumab (TCZ) and methotrexate (MTX) combination therapy 8mg/kg 4-weekly for a total of 48 weeks. Receives: Drug: Tocilizumab; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK).
Changes up to week 60
Measured: To week 60
Secondary outcomes (8)
Reduction in inflammation in each treatment arm using ultrasound
Establish reduction in inflammation in each treatment arm using ultrasound using grey scale power doppler
Measured: To week 48
Disease Activity Score (DAS): DAS28/44 remission
Proportion of patients achieving DAS28/44 remission
Measured: To week 48
Questionnaires and research tools
Using tools including DAS28/44, SDAI, CDAI
Measured: Week 48
Health Assessment Questionniaire (HAQ) scores
The change from baseline in HAQ scores.
Measured: To week 48
VAS scores questionnaire
The change in VAS scores for pain, disease activity
Measured: To week 48
Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire
The change in RAQoL from baseline
Measured: To week 48
Bone densitometry
Bone densitometry scan of hands, spine, femoral neck
Measured: Week 48.
Sharp score on plain radiographs
Change in modified Sharp score on plain radiographs
Measured: Week 48.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study startMay 2013
- Primary completion29 Mar 2016
- Study completion29 Mar 2016
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
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Principal investigator, Dr Maya Buch, University of Leeds
- Investigators
- Dr Maya H Buch, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157010
- Sponsor's protocol ID
- RR11/9965
- Other IDs
- 2011-004017-17, 14383
- Acronym
- TREMERA
- Status last verified
- Nov 2019
- First submitted
- 15 Apr 2014
- Last updated
- 8 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single-centre, Open-Label, Randomised, Pilot Study Assessing the Changes in Expression of Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) and Speed & Depth of Remission Induced by Tocilizumab & Methotrexate Combination and Tocilizumab Monotherapy in Patients With Early Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT04157010
- Acronym / sponsor ID
- TREMERA / RR11/9965
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- May 2013
- Primary completion
- 29 Mar 2016 (actual)
- Study completion
- 29 Mar 2016 (actual)
- First posted
- 8 Nov 2019 (actual)
- 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.
The TREMERA study focuses on patients with newly diagnosed, untreated, rheumatoid arthritis (RA). Recent international treatment recommendations emphasise the need to diagnose RA early and start treatment immediately (this being associated with better response rates); and to aim for the goal of remission i.e. the absence of signs and symptoms of active inflammatory disease activity which is associated with better outcomes for the patient. Remission is more achievable with significant treatment advances that have been made in the form of highly effective biologic therapies. Tocilizumab (TCZ) is a newly introduced biologic drug that is used in established RA. The TREMERA study primarily aims to investigate the biological changes seen in blood and tissue following TCZ therapy this will contribute to a better understanding of how the drug works as well as disease processes; and will also identify whether administering a biologic drug such as TCZ can also switch off immunological parameters associated with a disrupted immune system of RA. The study will assess the effectiveness of TCZ given on its own or in combination with methotrexate (MTX; a standard therapy usually given with biologic treatments)in patients with early onset RA to determine the proportion that achieve remission. This study also aims to find out how quickly remission can be achieved with TCZ and the depth of remission achieved. This will be done using usual clinical assessment but also imaging such as ultrasound and magnetic resonance imaging (MRI) which can detect inflammation not apparent on clinical assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TCZ monotherapy | Experimental | Drug: TocilizumabTocilizumab (TCZ) monotherapy 8mg/kg 4-weekly for a total of 48 weeks. |
| TCZ+MTX combination therapy | Experimental | Drug: Tocilizumab, Drug: MethotrexateTocilizumab (TCZ) and methotrexate (MTX) combination therapy 8mg/kg 4-weekly for a total of 48 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of rheumatoid arthritis (2010 ACR/EULAR RA classification criteria)
- Symptom duration ≤12months
- No previous disease modifying antirheumatic drug (DMARD) therapy
- Active RA at baseline (defined as: DAS28 ≥ 3.2)
- Active hand and/or wrist joint evaluable by US and MRI (with no planned surgery during the study period)
Key exclusion criteria (7 listed)
- Patients unwilling or unable to receive MTX for the duration of the study.
- Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosis, or any arthritis with onset prior to 16 years of age.
- Suspicion of diagnosis of tuberculosis (TB): positive quantiferon +/abnormal chest x-ray, as per clinician judgement. Prior history of TB with confirmed full chemotherapy +/latent TB adequately treated may be included as per physician's discretion.
- Intramuscular, oral or intraarticular (of non-target joint) corticosteroid within 28 days of the screening visit; intra-articular steroid of the chosen target joint within 12 weeks of screening.
- Patients with serious infections within 3 month of enrolment (screening) or persistent infections.
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 |
|---|---|---|
| Tocilizumab | Drug | TCZ monotherapy, TCZ+MTX combination therapy |
| Methotrexate | Drug | TCZ+MTX combination therapy |
Primary outcome
Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK).
Time frame: To week 60
Changes up to week 60
8 secondary outcomes
Reduction in inflammation in each treatment arm using ultrasound
Time frame: To week 48
Disease Activity Score (DAS): DAS28/44 remission
Time frame: To week 48
Questionnaires and research tools
Time frame: Week 48
Health Assessment Questionniaire (HAQ) scores
Time frame: To week 48
VAS scores questionnaire
Time frame: To week 48
Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire
Time frame: To week 48
Bone densitometry
Time frame: Week 48.
Sharp score on plain radiographs
Time frame: Week 48.
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 8 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.
Dr Maya H Buch 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 Tocilizumab and Methotrexate in people with Rheumatoid 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 6 inclusion and 7 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 8 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. 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?
Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK). (time frame: To week 60). 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 8 Nov 2019; AzTrials last refreshed its copy on 31 Oct 2026.