Validation Study of RA-INF-Dx, a Multigene Molecular Test Used to Predict Non-Response to INfliximab Therapy (PRINT)

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 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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis

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.

• Study Type: Observational
• Enrollment (Actual): 123

Contacts and Locations

Study Locations

• Canada
  • Mississauga - Chow, Canada
    • Location n°31
  • Ontario, Canada
    • Location n°36
  • Rimouski, Canada
    • Location n°34
  • Saskatchewan, Canada
    • Location n°33
  • Toronto, Canada
    • Location n°35
• France
  • Amiens, France
    • Location n°41
  • Bobigny, France
    • Location n°13
  • Dreux, France
    • Location n°39
  • Grenoble, France
    • Location n°14
  • Meaux, France
    • Location n°40
  • Paris, France
    • Location n°25
  • Paris (Hop Bichat), France
    • Location n°37
  • Strasbourg, France
    • Location n°38
• Hungary
  • Budapest, Hungary
    • Location n°6
  • Budapest, Hungary
    • Location n°8
  • Debrecen, Hungary
    • Location n°7
  • Eger, Hungary
    • Location n°10
  • Kistarcsa, Hungary
    • Location n°9
• Italy
  • Messina, Italy
    • Location n°15
  • Milano, Italy
    • Location n°16
  • Pisa, Italy
    • Location n°17
• Lithuania
  • Kaunas, Lithuania
    • Location n°27
  • Klaipeda, Lithuania
    • Location n°29
  • Panevezys, Lithuania
    • Location n°30
  • Vilnius, Lithuania
    • Location n°28
• Romania
  • Bucharest, Romania
    • Location n° 19
  • Bucharest, Romania
    • Location n°20
  • Bucharest, Romania
    • Location n°22
  • Bucharest, Romania
    • Location n°23
  • Cluj Napoca, Romania
    • Location n°21
  • Iasi, Romania
    • Location n°24
  • Iasi, Romania
    • Location n°26
  • Timisoara, Romania
    • Location n°18
• Slovakia
  • Banska Bystrica, Slovakia
    • Location n°12
  • Piestany, Slovakia
    • Location n°11
• Spain
  • Malaga, Spain
    • Location n°3
  • Oviedo, Spain
    • Location n°5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
a single group of patients -200 expected; polyarthrite rhumatoid patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Statistical relationship between the RA-INF-Dx blood test results and the non-response (evaluated according to EULAR criteria) to infliximab and methotrexate combination therapy will be analyzed.	Performed at inclusion : blood samples will be taken before the infliximab infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-response to infliximab and methotrexate combination therapy based on American College of Rheumatology (ACR) criteria	A statistical analysis will be performed in order to evaluate the predictive performances of the test validated in the study primary objective in relation to the non-response to infliximab and methotrexate combination therapy evaluated according to ACR criteria.	at the time of the first response evaluation (between the 12th and the 14th week)

Collaborators and Investigators

• Sponsor: TcLand Expression S.A.
• Collaborators: Premier Research Group plc; Theradis pharma; Medpharmgene, Inc.
• Investigators: Principal Investigator: Sara MARSAL, MD, University Hospital Val d'Hebron (Barcelona, Spain)

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimate): February 18, 2011

Study Record Updates

• Last Update Posted (Estimate): February 1, 2013
• Last Update Submitted That Met QC Criteria: January 31, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Methotrexate; Rheumatoid Arthritis; DMARDs; Infliximab; Anti TNF; Gene expression biomarkers
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 2010-A01046-33