Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
286
Countries
1
Sites
21
Rheumatoid Arthritis
To demonstrate whether or not targeted therapies are more effective than triple therapies in methotrexate or leflunomide-IR patients with RA.
Key facts
- Sponsor
- Les Hopitaux Universitaires De Strasbourg
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 30 Mar 2016 → ongoing
- Decision date (initial)
- 2024-10-16
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-516704-41-00
- EudraCT number
- 2015-000863-15
- ClinicalTrials.gov
- NCT02714634
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To demonstrate whether or not targeted therapies are more effective than triple therapies in methotrexate or leflunomide-IR patients with RA.
Secondary objectives 10
- To compare the safety profile of the two strategies
- To compare the drug retention rate of the two strategies and the adhesion to treatment at inclusion, 6, and 12 months.
- To compare the change in the clinical disease activity index (CDAI) of the two strategies at 3, 6, 9 and 12 months.
- To compare the DAS 28 CRP of the two strategies at 3, 6, 9 and 12 months.
- To compare the ACR of the two strategies and the boolean remission at 3, 6, 9 and 12 months.
- To compare the radiographic progression of the two strategies between 0 and 12 months.
- To compare the change of comedications at 3, 6, 9 and 12 months.
- To compare the patient quality of life and fatigue in the two groups.
- To assess the impact of rheumatoid arthritis on sexuality in the two groups.
- To assess and compare medico-economic aspects in the two groups.
Conditions and MedDRA coding
Rheumatoid Arthritis
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomised and controlled Trial METHOTREXATE OR LEFLUNOMIDE + TARGETED THERAPY or METHOTREXATE OR LEFLUNOMIDE + SULFASALAZINE + HYDROXYCHLOROQUINE
|
Randomised Controlled | None | METHOTREXATE OR LEFLUNOMIDE + TARGETED THERAPY: administration of METHOTREXATE OR LEFLUNOMIDE + TARGETED THERAPY METHOTREXATE OR LEFLUNOMIDE + SULFASALAZINE + HYDROXYCHLOROQUINE: Administration of METHOTREXATE OR LEFLUNOMIDE + SULFASALAZINE + HYDROXYCHLOROQUINE |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- 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 and/or 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
- Affiliation to a social insurance system
- Women of child bearing potential, negative β-HCG assay (blood test)
- 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).
Exclusion criteria 13
- Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)*
- Previous treatment with or contraindication to triple therapy*
- Other inflammatory arthritis except those associated to 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 for patients in the biologic arm
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg of equivalent prednisone under the randomized strategy after, at least, 11 months of follow up.
Secondary endpoints 10
- Serious adverse events rate
- 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 at 6, and 12 months
- Clinical disease activity index (CDAI) at inclusion, 3, 6, 9 and 12 months
- DAS 28 CRP score at inclusion, 3, 6, 9 and12 months
- 52010 ACR/EULAR classification Criteria for RA, ACR 20, 50, 70 and Boolean remission at 3, 6, 9 and 12 months
- Modified Sharp Van der Hejde score at inclusion and at 12 month
- Change in comedications (corticosteroids, dose of methotrexate or leflunomide, subcutaneous use of methotrexate), treatment observance
- SF36 score, Rapid score, HAQ score, RAID score, FACIT score at inclusion, 3, 6, 9 and at 12 months
- QUALISEX score at inclusion, 6 months and at 12 months
- Medico-economic evaluation results at inclusion, 3, 6, 9 and at 12 months
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 19
SUB20313 · Substance
- Active substance
- Tocilizumab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 9600 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12570MIG · Substance
- Active substance
- Rituximab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 4000 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02681MIG · Substance
- Active substance
- Infliximab
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 7.5 mg/kg milligram(s)/kilogram
- Max total dose
- 49.5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25423 · Substance
- Active substance
- Certolizumab Pegol
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 6000 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB33104 · Substance
- Active substance
- Tofacitinib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 11 mg milligram(s)
- Max total dose
- 4015 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25638 · Substance
- Active substance
- Golimumab
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED PEN
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20635 · Substance
- Active substance
- Abatacept
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Max daily dose
- 12.5 mg/kg milligram(s)/kilogram
- Max total dose
- 187.5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB01984MIG · Substance
- Active substance
- Etanercept
- Pharmaceutical form
- POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 2600 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10727MIG · Substance
- Active substance
- Sulfasalazine
- Pharmaceutical form
- GASTRO-RESISTANT TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2 g gram(s)
- Max total dose
- 730 g gram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB182273 · Substance
- Active substance
- Filgotinib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 73 g gram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB180983 · Substance
- Active substance
- Baricitinib
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 1460 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20016 · Substance
- Active substance
- Adalimumab
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 1040 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08424MIG · Substance
- Active substance
- Leflunomide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 7540 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1300 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- TABLETS
- Route of administration
- ORAL USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1300 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1300 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB187251 · Substance
- Active substance
- Upadacitinib
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 15 mg milligram(s)
- Max total dose
- 5475 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02587MIG · Substance
- Active substance
- Hydroxychloroquine Sulfate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 219 g gram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB177914 · Substance
- Active substance
- Sarilumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 5200 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Les Hopitaux Universitaires De Strasbourg
- Sponsor organisation
- Les Hopitaux Universitaires De Strasbourg
- Address
- 1 Place De L Hopital, Cs 80426 Cs 80426
- City
- Strasbourg Cedex
- Postcode
- 67091
- Country
- France
Scientific contact point
- Organisation
- Les Hopitaux Universitaires De Strasbourg
- Contact name
- Jacques-Eric GOTTENBERG
Public contact point
- Organisation
- Les Hopitaux Universitaires De Strasbourg
- Contact name
- Jacques-Eric GOTTENBERG
Locations
1 EU/EEA country · 21 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 270 | 21 |
| Rest of world
Monaco
|
— | 16 | — |
Investigational sites
Centre Hospitalier Universitaire De Poitiers
Rheumatology, 2 Rue De La Miletrie, 86000, Poitiers
Assistance Publique Hopitaux De Paris
Rheumatology, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
Groupe Hospitalier Du Havre
rheumatology, Avenue Pierre Mendes France, 76290, MONTIVILLIERS
Centre Hospitalier Universitaire De Montpellier
Rheumatology, 371 Avenue Du Doyen Gaston Giraud, 34091, Montpellier Cedex 5
Assistance Publique Hopitaux De Paris
Rheumatology, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Regional Et Universitaire De Brest
Rheumatology, Boulevard Tanguy Prigent, 29200, Brest
Centre Hospitalier Universitaire De Saint Etienne
Rheumatology, Avenue Albert Raimond, 42270, Saint Priest En Jarez
Centre Hospitalier Universitaire De Nantes
Rheumatology, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Universitaire De Caen Normandie
Rheumatology, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Assistance Publique Hopitaux De Paris
Rheumatology, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
Centre Hospitalier Universitaire Grenoble Alpes
Rheumatology, Av De Kimberley, Bp 185, Echirolles
Centre Hospitalier Departemental Vendee
Rheumatology, Boulevard Stephane Moreau, 85925, La Roche Sur Yon Cedex 9
Les Hopitaux Universitaires De Strasbourg
Rheumatology, 1 Place De L Hopital, Cs 80426, Strasbourg Cedex
Centre Hospitalier Universitaire Rouen
Rheumatology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Universitaire De Toulouse
Rheumatology, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre Hospitalier Jean Rougier
Rheumatology, 52 Place Antonin Bergon, Bp 50269, Cahors
CHU Besancon
Rheumatology, 3 Boulevard Alexandre Fleming, 25000, Besancon
Centre Hospitalier Universitaire D Orleans
Rheumatology, 14 Avenue De L Hopital, Cs 86709, Orleans Cedex 2
Assistance Publique Hopitaux De Paris
Rheumatology, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Groupement Des Hopitaux De L'Institut Catholique De Lille
Rheumatology, 115 Rue Du Grand But, Bp 50249 Lille, Lomme Cedex
Centre Hospitalier Universitaire De Bordeaux
Rheumatology, Place Amelie Raba Leon, 33000, Bordeaux
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2016-03-30 | 2016-03-30 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 23 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-516704-41-00 | 7.2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF_Majeur | 6.1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC ARAVA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC CIMZIA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC ENBREL | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC HUMIRA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC JYSELECA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC KEVZARA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC MABTHERA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC METHOTREXATE BIODIM INJ | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC METOJECT | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC NOVATREX | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC OLUMIANT | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC ORENCIA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC PLAQUENIL | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC REMICADE | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC RINVOQ | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC ROACTEMRA | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC SALAZOPYRINE | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC SIMPONI | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC XELJANZ | 2 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_FR 2024-516704-41-00 | 7.2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-19 | France | Acceptable 2024-09-19
|
2024-10-16 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-12-18 | France | Acceptable 2025-01-27
|
2025-02-14 |