RABIOPRED - a Validation Study of Theranostic Test to PREDict Treatment Response of Anti-TNFα BIologicals in Rheumatoid Arthritis

Study Overview
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Brief Summary
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RABIOPRED is an in vitro non-invasive blood test, which aims to identify patients with rheumatoid arthritis (RA) who are not likely to respond to anti-TNFα and methotrexate combination therapy.

Detailed Description
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Multi-centre, non-interventional, open-label, non-comparative, prospective cohort study with a clinical follow-up between (a) 12 and 14 weeks and (b) 22 and 24 weeks. The RABIOPRED test is indicated for use in patients: 18 years of age or older, Eligible for a first line biologic therapy with anti-TNF alpha. The RABIOPRED test is indicated for use by rheumatologists as a biological basis for guiding anti-TNF alpha treatment prior to its initiation.

Official Title
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Proof-of-Performance Study of RABIOPRED Assay as an In Vitro Diagnostic Test to Identify Patients With Rheumatoid Arthritis Who Are Unlikely to Show Response to 1st Treatment With Anti-TNFα and Methotrexate Combination.

Conditions
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RheumatoId Arthritis

Intervention / Treatment
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* Biological: Infliximab
* Biological: Adalimumab
* Biological: Etanercept
* Biological: Golimumab
* Biological: Certolizumab Pegol
* Biological: Infliximab biosimilar
* Biological: Etanercept biosimilar
* Biological: Infliximab biosimilar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with a confirmed Rheumatoid Arthritis according the American College of Rheumatology (ACR) classification criteria (Arnett FC, 1988, Arthritis Rheum) Patient with a DAS28 index greater than 3.2. Patient eligible for treatment with an anti-TNFα agent (any one of Remicade®, Humira®, Enbrel®, Simponi®, Cimzia®, Remsima®/Inflectra®, Benepali® and Flixabi® according to the Summary of Product Characteristics for each product) and Methotrexate combination therapy, Patient refractory to treatment with at least one classical DMARDs (one of which has to be MTX) prescribed according to the international recommendations, i.e. for at least 12 weeks at the maximal tolerated dose prior to anti-TNFα treatment and with doses which must have been kept stable during the 4 weeks preceding the initiation of the anti-TNFα therapy. In case of Leflunomide treatment, patients may be included in the study after a period of at least 3 months of Leflunomide stop, or after a washout by cholestyramine for at least 11 days. Use of oral steroids (≤ 10 mg/day of prednisone or equivalent dose of another molecule) and/or NSAIDs will be permitted; doses must have been kept stable during the 4 weeks preceding the initiation of the anti-TNFα therapy Patient (male or female) at 18 years of age or older at inclusion, Negative β-HCG (Human Chorionic Gonadotrophin) pregnancy test, when appropriate, according to the patient's age and contraceptive method. Written Informed consent signed from the patient. Exclusion Criteria: Patient having received previously any anti-TNFα biologic therapy or any molecule in development belonging to anti-TNFα class. Patients having received other biologics (such as anti-CD20, anti-CTLA4, IL1 blockers, IL6 blockers and other molecules in development) can be included in the study after a period of at least 6 months, Patient non eligible to anti-TNFα according to the SmPC (Summary of Products), Patient on anti-TNFα monotherapy without methotrexate, Patient with clinically significant, severe and uncontrolled infectious diseases, Patient with symptoms of a significant somatic or psychiatric/mental illness, Patient with other auto-immune diseases (i.e. Inflammatory Bowel Diseases, Systemic Lupus Erythematosus, vasculitis, uncontrolled asthma, etc.), Patient with evidence of cardiac, pulmonary, metabolic, renal, hepatic, gastro-intestinal conditions, which, in the opinion of the Investigator, may interfere with the study, Cancer, Pregnancy, Nursing mothers, Patient who is participating in a clinical trial of other biologics or for whom a period of exclusion has been defined

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infliximab (Remicade®)<br> | Biological: Infliximab<br>* Anti-TNF alpha originator<br>* Other names: Remicade®;|
| Adalimumab (Humira®)<br> | Biological: Adalimumab<br>* Anti-TNF alpha originator<br>* Other names: Humira®;|
| Etanercept (Enbrel®)<br> | Biological: Etanercept<br>* Anti-TNF alpha originator<br>* Other names: Enbrel®;|
| Golimumab (Simponi®)<br> | Biological: Golimumab<br>* Anti-TNF alpha originator<br>* Other names: Simponi®;|
| Certolizumab Pegol (Cimzia®)<br> | Biological: Certolizumab Pegol<br>* Anti-TNF alpha originator<br>* Other names: Cimzia®;|
| Infliximab biosimilar (Remsima®/ Inflectra®)<br> | Biological: Infliximab biosimilar<br>* Anti-TNF alpha Infliximab biosimilars<br>* Other names: Remsima® or Inflectra®;|
| Etanercept biosimilar (Benepali®)<br> | Biological: Etanercept biosimilar<br>* Anti-TNF alpha Etanercept biosimilar<br>* Other names: Benepali®;|
| Infliximab biosimilar (Flixabi®)<br> | Biological: Infliximab biosimilar<br>* Anti-TNF alpha Infliximab biosimilar<br>* Other names: Flixabi®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EULAR response criteria | Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 13th week (+/- 7 days) compared with baseline. | 13th week (+/- 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR response criteria | Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on ACR (American College of Rheumatology) response criteria at 13th week (+/- 7 days) compared with baseline. | 13th week (+/- 7 days) | 
| EULAR response criteria | Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline. | 23rd week (+/- 7 days) or at the time of treatment switch | 
| SDAI (Simplified Disease Activity Index) score | Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on achieving Low Disease Activity (LDA) according to SDAI score at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline. | 23rd week (+/- 7 days) or at the time of treatment switch | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Anti TNF, Infliximab, Adalimumab, Etanercept, Golimumab, Certolizumab Pegol, Infliximab biosimilar, Etanercept biosimilar, Methotrexate