Rheumatoid ArthritisPhase 4BIO3NCT02714634
Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide
A Phase 4 study testing Methotrexate + targeted therapy administration and methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration in people with Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide, run by University Hospital, Strasbourg, France at 1 site in France.
Trial summary
Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis, Insufficient Response to Methotrexate or Leflunomide
- What is being tested?
- Methotrexate + targeted therapy administration and methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 286 participants
- Where
- 1 siteFrance
- Study dates
- 30 Mar 2016to Mar 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
- DAS28-CRP>3.2
- Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment
- RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
- Age greater or equal to 18 years
- Written informed consent, dated and signed before initiating any trial-related procedure
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- Affiliation to a social insurance system
- Women of child bearing potential, negative β-HCG assay (Human chorionic gonadotropin)
- Effective method of birth control during the study and continuing after the discontinuation of the investigational drug or study. The duration will depend on the drug used (referred to the summary product characteristic).
Who cannot join
- Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)
- Previous treatment with triple therapy
- Other inflammatory arthritis except RA associated with Sjögren's syndrome
- Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine
- Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
- Absence of tuberculosis screening
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- Patient who cannot be followed during 12 months
- Pregnancy, breastfeeding, desire of pregnancy in the 12 months
- Drug addiction, addiction to alcohol
- Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
- Women of child bearing potential, unless they are using an effective method of birth control
- Patient under law protection
- Prisoners
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jacques-Eric GOTTENBERG, Professor contact
France1 site, 1 recruiting
- Recruiting
Hôpitaux Universitaires de Strasbourg
Strasbourg, 67098
Jacques-Eric Gottenberg, 3 88 12 81 89 ext. 0033, jacques-eric.gottenberg@chru-strasbourg.fr
Jacques-Eric Gottenberg
About this study
Official title: Randomized Controlled Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide
Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.
- Being tested
- Methotrexate + targeted therapy administration, methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methotrexate + targeted therapy administrationDrug
- Methotrexate or leflunomide + adalimumab or
- Methotrexate or leflunomide + certolizumab or
- Methotrexate or leflunomide + etanercept or
- Methotrexate or leflunomide + golimumab or
- Methotrexate or leflunomide + infliximab or
- Methotrexate or leflunomide + abatacept or
- Methotrexate or leflunomide + rituximab or
- Methotrexate or leflunomide + tocilizumab or
- Methotrexate or leflunomide + sarilumab or
- Methotrexate or leflunomide + filgotinib or
- Methotrexate or leflunomide + upadacitinib or
- Methotrexate or leflunomide + Tofacitinib or
- Methotrexate or leflunomide + baricitinib
methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administrationDrug
| Study group | Role | What they receive |
|---|---|---|
| methotrexate + targeted therapy group | Experimental | Methotrexate or leflunomide +
targeted therapy chosen by investigator Receives: Drug: Methotrexate + targeted therapy administration |
| Triple therapy | Active comparator | Triple therapy using 3 conventional disease modifying drugs (DMARDs) Receives: Drug: methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone
Measured: At 12 months
Secondary outcomes (12)
Serious adverse events rate
Measured: At 3, 6, 9 and at 12 months
Blood concentrations of hydroxychloroquine, leflunomide, sulfasalazine and methotrexate in the triple therapy group and methotrexate, leflunomide, biologic / JAK/STAT inhibitor and anti-drug antibody in the other group.
Measured: at 6, and 12 months
Clinical disease activity index (CDAI).
Measured: At inclusion, 3, 6, 9 and 12 months
DAS 28 CRP score.
Measured: at inclusion, 3, 6, 9 and 12 months.
2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission.
Measured: at 3, 6, 9 and 12 months.
Modified Sharp Van der Heijde score.
Measured: at inclusion and at 12 months
Change in comedications (dose)
Measured: at 3, 6, 9 and 12 months
Change in comedications (route of administration)
Measured: at 3, 6, 9 and 12 months
Change in comedications (drug)
Measured: at 3, 6, 9 and 12 months
QUALISEX score at inclusion, 6 months and at 12 months.
Measured: at inclusion, 6 months and at 12 months.
Medico-economic costs.
Measured: at inclusion, 3, 6, 9 and at 12 months.
Treatment compliance
A questionnaire will be filled by patient
Measured: at 3, 6, 9 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2016 (estimated)
- Study start30 Mar 2016
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
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.
- More trials run by University Hospital, Strasbourg, FranceThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 286 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02714634
- Sponsor's protocol ID
- 6020
- Acronym
- BIO3
- Status last verified
- Mar 2025
- First submitted
- 1 Feb 2016
- Last updated
- 12 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide
- ClinicalTrials.gov ID
- NCT02714634
- Acronym / sponsor ID
- BIO3 / 6020
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 286 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 21 Mar 2016 (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.
Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| methotrexate + targeted therapy group | Experimental | Drug: Methotrexate + targeted therapy administrationMethotrexate or leflunomide + targeted therapy chosen by investigator |
| Triple therapy | Active comparator | Drug: methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administrationTriple therapy using 3 conventional disease modifying drugs (DMARDs) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
- DAS28-CRP>3.2
- Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment
- RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
- Age greater or equal to 18 years
Key exclusion criteria (13 listed)
- Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)
- Previous treatment with triple therapy
- Other inflammatory arthritis except RA associated with Sjögren's syndrome
- Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine
- Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
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 |
|---|---|---|
| Methotrexate + targeted therapy administration* Methotrexate or leflunomide + adalimumab or * Methotrexate or leflunomide + certolizumab or * Methotrexate or leflunomide + etanercept or * Methotrexate or leflunomide + golimumab or * Methotrexate or leflunomide + infliximab or * Methotrexate or leflunomide + abatacept or * Methotrexate or leflunomide + rituximab or * Methotrexate or leflunomide + tocilizumab or * Methotrexate or leflunomide + sarilumab or * Methotrexate or leflunomide + filgotinib or * Methotrexate or leflunomide + upadacitinib or * Methotrexate or leflunomide + Tofacitinib or * Methotrexate or leflunomide + baricitinib | Drug | methotrexate + targeted therapy group |
| methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration | Drug | Triple therapy |
Primary outcome
Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone
Time frame: At 12 months
12 secondary outcomes
Serious adverse events rate
Time frame: At 3, 6, 9 and at 12 months
Blood concentrations of hydroxychloroquine, leflunomide, sulfasalazine and methotrexate in the triple therapy group and methotrexate, leflunomide, biologic / JAK/STAT inhibitor and anti-drug antibody in the other group.
Time frame: at 6, and 12 months
Clinical disease activity index (CDAI).
Time frame: At inclusion, 3, 6, 9 and 12 months
DAS 28 CRP score.
Time frame: at inclusion, 3, 6, 9 and 12 months.
2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission.
Time frame: at 3, 6, 9 and 12 months.
Modified Sharp Van der Heijde score.
Time frame: at inclusion and at 12 months
Change in comedications (dose)
Time frame: at 3, 6, 9 and 12 months
Change in comedications (route of administration)
Time frame: at 3, 6, 9 and 12 months
Change in comedications (drug)
Time frame: at 3, 6, 9 and 12 months
QUALISEX score at inclusion, 6 months and at 12 months.
Time frame: at inclusion, 6 months and at 12 months.
Medico-economic costs.
Time frame: at inclusion, 3, 6, 9 and at 12 months.
Treatment compliance
Time frame: at 3, 6, 9 and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Jacques-Eric GOTTENBERG, Professor contact
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 Methotrexate + targeted therapy administration and methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration in people with Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide, run by University Hospital, Strasbourg, France at 1 site in France.
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 9 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 12 Mar 2025. 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 France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jacques-Eric GOTTENBERG, Professor (3 88 12 79 53 ext. +33, jacques-eric.gottenberg@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone (time frame: At 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 12 Mar 2025.