SpondyloarthritisMESYNADNCT04360785
Effect of Two Methotrexate in Sync With the First Adalimumab to Prevent the Immunisation Anti Ada in Spondyloarthritis
A study testing Methotrexate in people with Spondyloarthritis, run by Assistance Publique - Hôpitaux de Paris at 17 sites in France.
Trial summary
Preliminary report have demonstrated that methotrexate induces an anti bio-medicament tolerization whan administrated just before the first administration of the bio-medicament. Once this tolerization is obtained it seems useless to continue the methotrexate because this treatment has no efficacity in cases of… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Spondyloarthritis
- What is being tested?
- Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 17 sitesFrance
- Study dates
- 11 Nov 2020to 27 Feb 2023
- Phase
- Interventional
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged from 18 to 90
- Patients suffering from axial SpA, radiographic or non-radiographic according to ASAS criteria (peripheral involvement and/or Inflammatory bowel diseases could be present).
- Indication for anti TNF treatment: resistance to at least 2 NSAIDs and no contraindication to adalimumab
- No previous treatment with methotrexate in the last 3 months
- Stable dosage of steroids (less than 10mg/day of prednisone equivalent) and/or of NSAIDs for at least 10 days
- Contraception feminine or masculine
- Informed and written consent
- Social insurance
Who cannot join
- Contraindication to methotrexate
- Previous treatment with adalimumab
- Steroids more than 10mg/day of prednisone equivalent
- Previous treatment with:
- Etanercept in the last month
- Infliximab, golimumab, certolizumab in the last 2 months (Previous treatment hereafter these dates with anti-TNF except adalimumab or secukinumab are not a counterindication)
Show all 10Show fewer
- Current immunosuppressive drugs except methotrexate
- Current and proven pregnancy
- Project of pregnancy in the next 3 months following inclusion
- Legal safeguards
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
Hopital Pellegrin
Bordeaux
Hopital Ambroise Paré
Boulogne-Billancourt
Hopital La Cavale Blanche
Brest
CHU Trousseau
Chambray-lès-Tours
CH Sud Francilien
Corbeil-Essonnes
Hopital Mondor
Créteil
Kremlin Bicetre hospital
Le Kremlin-Bicêtre
CH Le Mans
Le Mans
Hopital Saint Philibert
Lille
CHU Nantes
Nantes
CHR Orléans
Orléans
Hopital Bichat
Paris
Hopital Cochin
Paris
Hopital la Pitié Salpétrière
Paris
Hopital Saint Antoine
Paris
CH Pontoise
Pontoise
CHU Rouen
Rouen
About this study
Official title: Effect of Two Methotrexate Injections in Sync With the First Adalimumab Injection to Prevent the Immunisation Anti Adalimumab During Treatment of Spondyloarthritis
Preliminary report have demonstrated that methotrexate induces an anti bio-medicament tolerization whan administrated just before the first administration of the bio-medicament. Once this tolerization is obtained it seems useless to continue the methotrexate because this treatment has no efficacity in cases of spondyloarthritis.
Read the detailed description
spondyloarthritis are treated in first intention by NSAIDs but in case of inefficacity biotherapies that inhib the TNF are used. Adalimumab is the most used anti TNF in this indication. Monoclonal antibody uses in therapy is immunogene, and there is a clear link between increase of anti drug antibody and in one hand decrease of drug serum concentration and in an other failure of the therapeutic response. With adalimumab there is an apparition of ADAb in 30%. There are reports suggesting that adding methotrexate to the therapy in a specific timeline allow to prevent the immunization. A previous study shows that association in long terms between methotrexate and adalimumab induce less immunized patients. The investigator's goal is to assess if two methotrexate subcutaneous injections at day 1 and 2 could prevent anti adalimumab antibodies formation.
- Conditions
- Spondyloarthritis
- Being tested
- Methotrexate
- Keywords
- adalimumab, anti-drug antibodies, tolerization, methotrexate, spondyloarthritis
- Medical subject headings
- Spondylarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Patients randomized in this arm will have one subcutaneous injection of methotrexate 15min before and one 24h after their first injection of adalimumab prescribed as usual
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate + Adalimumab | Experimental | Experimental group : patients will receive 2 subcutaneous injections of methotrexate in addition of the usual adalimumab Receives: Drug: Methotrexate |
| Adalimumab | No intervention | Reference group : patient will receive adalimumab as usual to treat spondyloarthritis |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum concentrations of ADAb anti adalimumab
To assess if 2 subcutaneous injections of methotrexate could prevent anti adalimumab antibodies formation at month 6 in patients with spondyloarthritis
Measured: 6 month
Secondary outcomes (7)
residual serum concentration of adalimumab
To compare trough levels of adalimumab at month 1, 3, 6 and 12 in the 2 groups.
Measured: At 1, 3, 6 and 12 months
serum concentrations of ADAb anti adalimumab
To compare the percentage of immunized patients at month 1, 3 and 12 in the 2 groups
Measured: At 1, 3 and 12 months
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events as assessed by the number of AE and SAE related to the treatment that occur during the participation of the patient
Measured: At 1, 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
A therapeutic efficacity will be described as a clinical pertinent change of ASDAS : Ankylosing Spondylitis Disease Activity Score (at least 1,1 point) (a higher score means a worse outcome)
Measured: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
A therapeutic efficacity will be described as a clinical pertinent change of BASDAI : Bath Ankylosing Spondylitis Disease Activity Index (0 to 50 points - a higher score means a worse outcome)
Measured: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
Assess by Number of patient who didn't switch treatment
Measured: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
Assess by ASAS-NSAIDS score (Assessment of SpondyloArthritis international Society - nonsteroidal antiinflammatory drugs) (minimum 0. a higher score means a worse outcome)
Measured: At 3, 6 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 posted24 Apr 2020
- Study start11 Nov 2020
- Primary completion13 Sep 2022
- Study completion27 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SpondyloarthritisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- gaetane Nocturne, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04360785
- Sponsor's protocol ID
- APHP180571
- Acronym
- MESYNAD
- Status last verified
- Apr 2023
- First submitted
- 2 Mar 2020
- Last updated
- 4 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Two Methotrexate Injections in Sync With the First Adalimumab Injection to Prevent the Immunisation Anti Adalimumab During Treatment of Spondyloarthritis
- ClinicalTrials.gov ID
- NCT04360785
- Acronym / sponsor ID
- MESYNAD / APHP180571
- Conditions
- Spondyloarthritis
- Keywords
- adalimumab, anti-drug antibodies, tolerization, methotrexate, spondyloarthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 11 Nov 2020 (actual)
- Primary completion
- 13 Sep 2022 (actual)
- Study completion
- 27 Feb 2023 (actual)
- First posted
- 24 Apr 2020 (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.
Preliminary report have demonstrated that methotrexate induces an anti bio-medicament tolerization whan administrated just before the first administration of the bio-medicament. Once this tolerization is obtained it seems useless to continue the methotrexate because this treatment has no efficacity in cases of spondyloarthritis.
Detailed description
spondyloarthritis are treated in first intention by NSAIDs but in case of inefficacity biotherapies that inhib the TNF are used. Adalimumab is the most used anti TNF in this indication. Monoclonal antibody uses in therapy is immunogene, and there is a clear link between increase of anti drug antibody and in one hand decrease of drug serum concentration and in an other failure of the therapeutic response. With adalimumab there is an apparition of ADAb in 30%. There are reports suggesting that adding methotrexate to the therapy in a specific timeline allow to prevent the immunization. A previous study shows that association in long terms between methotrexate and adalimumab induce less immunized patients. The investigator's goal is to assess if two methotrexate subcutaneous injections at day 1 and 2 could prevent anti adalimumab antibodies formation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate + Adalimumab | Experimental | Drug: MethotrexateExperimental group : patients will receive 2 subcutaneous injections of methotrexate in addition of the usual adalimumab |
| Adalimumab | No intervention | –Reference group : patient will receive adalimumab as usual to treat spondyloarthritis |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients aged from 18 to 90
- Patients suffering from axial SpA, radiographic or non-radiographic according to ASAS criteria (peripheral involvement and/or Inflammatory bowel diseases could be present).
- Indication for anti TNF treatment: resistance to at least 2 NSAIDs and no contraindication to adalimumab
- No previous treatment with methotrexate in the last 3 months
- Stable dosage of steroids (less than 10mg/day of prednisone equivalent) and/or of NSAIDs for at least 10 days
Key exclusion criteria (10 listed)
- Contraindication to methotrexate
- Previous treatment with adalimumab
- Steroids more than 10mg/day of prednisone equivalent
- Previous treatment with:
- Current immunosuppressive drugs except methotrexate
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 |
|---|---|---|
| MethotrexatePatients randomized in this arm will have one subcutaneous injection of methotrexate 15min before and one 24h after their first injection of adalimumab prescribed as usual | Drug | Methotrexate + Adalimumab |
Primary outcome
serum concentrations of ADAb anti adalimumab
Time frame: 6 month
To assess if 2 subcutaneous injections of methotrexate could prevent anti adalimumab antibodies formation at month 6 in patients with spondyloarthritis
7 secondary outcomes
residual serum concentration of adalimumab
Time frame: At 1, 3, 6 and 12 months
serum concentrations of ADAb anti adalimumab
Time frame: At 1, 3 and 12 months
Incidence of Treatment-Emergent Adverse Events
Time frame: At 1, 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using ASDAS (Ankylosing Spondylitis Disease Activity Score) score.
Time frame: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of Activity disease using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score.
Time frame: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of therapeutic maintenance
Time frame: At 3, 6 and 12 months
Comparison of Adalimumab Therapeutic efficacity in term of nonsteroidal anti inflammatory drugs ' reduction
Time frame: At 3, 6 and 12 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 4 Oct 2023.
- 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. This study is not recruiting at the moment.
gaetane Nocturne principal investigator
APHP
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methotrexate in people with Spondyloarthritis, run by Assistance Publique - Hôpitaux de Paris at 17 sites 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 8 inclusion and 10 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 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites 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.
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?
serum concentrations of ADAb anti adalimumab (time frame: 6 month). 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 4 Oct 2023.