Clinical trial NCT01299545: Validation Study of RA-INF-Dx, a Multigene Molecular Test Used to Predict Non-Response to INfliximab Therapy
Official title: Validation Study of RA-INF-Dx as a Multigene Molecular Test Intended to Aid in the Identification of Patients With Rheumatoid Arthritis Who Are Unlikely to Show an Initial Response to Infliximab and Methotrexate Combination Therapy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Anti TNF
Infliximab
Methotrexate
DMARDs
Gene expression biomarkers
Lead sponsor: TcLand Expression S.A.
Sponsor class: INDUSTRY
Collaborators: name: Premier Research Group plc
name: Theradis pharma
name: Medpharmgene, Inc.
First posted: 2011-02-18
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients suffering from RA eligible to a first biologic therapy for whom the treating rheumatologist envisages infliximab therapy will be included in this study.

Brief summary: Study Design \& Objectives:

Multi-centre, non-interventional, open-label, non-comparative, prospective cohort study with a clinical follow-up between 12 and 14 weeks.

To determine the performances of the RA-INF-Dx blood test intended to aid in the identification of patients with rheumatoid arthritis who are unlikely to show an initial response to infliximab and methotrexate combination therapy evaluated according to EULAR response criteria.

Ancillary study objective:

To constitute a biocollection of samples associated with all clinical and biological data collected at inclusion and at the evaluation visit.

Detailed description: The RA-INF-Dx test is a non invasive in vitro blood test intended to aid in the identification of patients with RA who are unlikely to show an initial response to infliximab and methotrexate combination therapy.

The RA-INF-Dx test is indicated for use in patients:

* 18 years of age or older,
* Eligible for a first line biologic therapy with infliximab. The RA-INF-Dx test is indicated for use by rheumatologists as a biological basis for guiding infliximab treatment prior to its initiation.

Eligibility criteria: Inclusion Criteria:

Diagnosis of Rheumatoid Arthritis

1. Patient with a confirmed Rheumatoid Arthritis according the American College of Rheumatology (ACR) classification criteria.

   Disease Activity
2. Patient with a DAS28 greater than 3.2.

   Treatment
3. Patient eligible for a first line TNFα blocking agent treatment with infliximab according to the "Summary of Product Characteristics",
4. 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 infliximab treatment and with doses which must have been kept stable during the 4 weeks preceding the initiation of the infliximab therapy (patients may be included if they have undergone a wash-out period using cholestyramine or equivalent subsequent to leflunomide treatment),
5. Use of oral steroids (≤ 10mg/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 infliximab therapy,

   Other criteria
6. Patient (male or female) at 18 years of age or older at inclusion,
7. Negative β-HCG pregnancy test, when appropriate according to the patient's age and contraceptive method,
8. Informed consent signed.

Exclusion Criteria:

1. Patient having received previous courses of other biologic therapy (TNF blocking agents, anti-CD20, anti-CTLA4, IL1 blockers, IL6 blockers and other molecules in development),
2. Patient non eligible to infliximab therapy according to the "Summary of Product Characteristics",
3. Patient with clinically significant, severe and uncontrolled infectious diseases,
4. Patient with symptoms of a significant somatic or psychiatric/mental illness,
5. Patient with other auto-immune diseases (i.e. Inflammatory Bowel Diseases, Systemic Lupus Erythematosus, vasculitis, uncontrolled asthma, etc...),
6. Patient with evidence of cardiac, pulmonary, metabolic, renal, hepatic, gastro-intestinal conditions, which, in the opinion of the investigator, may interfere with the study,
7. Pregnancy,
8. Patient that is participating in a clinical trial or that participated in a previous one within 10 weeks prior to study entry.

Primary outcomes:
measure: To determine the performances of the RA-INF-Dx test to aid in the identification of patients with RA who are unlikely to show an initial response to infliximab and methotrexate combination therapy.
timeFrame: Performed at inclusion : blood samples will be taken before the infliximab infusion.
Secondary outcomes:
measure: Non-response to infliximab and methotrexate combination therapy based on American College of Rheumatology (ACR) criteria
timeFrame: at the time of the first response evaluation (between the 12th and the 14th week)
Other outcomes:
Locations:
city: Mississauga - Chow
country: Canada
facility: Location n°31
city: Ontario
country: Canada
facility: Location n°36
city: Rimouski
country: Canada
facility: Location n°34
city: Saskatchewan
country: Canada
facility: Location n°33
city: Toronto
country: Canada
facility: Location n°35
city: Amiens
country: France
facility: Location n°41
city: Bobigny
country: France
facility: Location n°13
city: Dreux
country: France
facility: Location n°39
city: Grenoble
country: France
facility: Location n°14
city: Meaux
country: France
facility: Location n°40
city: Paris (Hop Bichat)
country: France
facility: Location n°37
city: Paris
country: France
facility: Location n°25
city: Strasbourg
country: France
facility: Location n°38
city: Budapest
country: Hungary
facility: Location n°6
city: Budapest
country: Hungary
facility: Location n°8
city: Debrecen
country: Hungary
facility: Location n°7
city: Eger
country: Hungary
facility: Location n°10
city: Kistarcsa
country: Hungary
facility: Location n°9
city: Messina
country: Italy
facility: Location n°15
city: Milano
country: Italy
facility: Location n°16
city: Pisa
country: Italy
facility: Location n°17
city: Kaunas
country: Lithuania
facility: Location n°27
city: Klaipeda
country: Lithuania
facility: Location n°29
city: Panevezys
country: Lithuania
facility: Location n°30
city: Vilnius
country: Lithuania
facility: Location n°28
city: Bucharest
country: Romania
facility: Location n° 19
city: Bucharest
country: Romania
facility: Location n°20
city: Bucharest
country: Romania
facility: Location n°22
city: Bucharest
country: Romania
facility: Location n°23
city: Cluj Napoca
country: Romania
facility: Location n°21
city: Iasi
country: Romania
facility: Location n°24
city: Iasi
country: Romania
facility: Location n°26
city: Timisoara
country: Romania
facility: Location n°18
city: Banska Bystrica
country: Slovakia
facility: Location n°12
city: Piestany
country: Slovakia
facility: Location n°11
city: Malaga
country: Spain
facility: Location n°3
city: Oviedo
country: Spain
facility: Location n°5
Study officials:
affiliation: University Hospital Val d'Hebron (Barcelona, Spain)
name: Sara MARSAL, MD
role: PRINCIPAL_INVESTIGATOR
References: