Immunogenicity and Safety of TNFa Kinoid in Rheumatoid Arthritis With Secondary Resistance to TNFa Antagonists

Inclusion Criteria:

• Diagnosis of RA according to the revised 1987 criteria of the American College ofRheumatology (ACR) (Arnett 1988) since at least six months prior to first studyproduct administration.

• Male or female between 18 and 70 years of age at the time of the first immunization

• Active RA disease as evidenced by a Disease Activity Score 28 (DAS 28) ≥ 3.2.

• Current or past treatment with an anti-TNF antagonist (infliximab,adalimumab,etanercept, certolizumab, golimumab).

• A wash-out period before the first administration of the study product of at least tenweeks since the last administration of certolizumab or golimumab; at least eigth weekssince the last administration of infliximab; at least four weeks since the lastadministration of adalimumab or etanercept

• History of positive response defined as an ACR20 or DAS 28 decrease ≥ 1.2 or by theinvestigator opinion with previous TNFα antagonist treatment.

• Secondary treatment failure to maximum one previous TNFα antagonist treatment asdefined by:

• Investigator opinion. OR

• DAS28 increase ≥ 0.6 during the last six months. OR

• Decrease in European League Against Rheumatoid (EULAR) score.

• Written informed consent .

Exclusion Criteria:

• Treatment with non-biological DMARDs within four weeks prior to first study productadministration. MTX is allowed provided it is administered at as table dosage < ou = 20 mg/week since at least 4 weeks.

• Treatment with any rheumatoid arthritis biological therapy other than TNFα antagonistsat any time prior to first study product administration.

• Administration of high doses of intra-articular corticosteroids for the treatment ofan acute mono-arthritis (eg knee) within 3 months prior to first study productadministration. High dose of corticosteroids is defined as > 50 mg triamcinolone orequivalent.

• History of documented severe bacterial infection within 28 days prior to firstimmunization

• History of primary resistance or intolerance to any TNFα antagonist.

• History of or current congestive heart failure, controlled or not.

• Corticosteroids (prednisone or equivalent, < ou = 10 mg per day) are allowed if theyare administered at stable dosage since at lesat 4 weeks prior to the firstimmunization. Inhaled and topical steroids are allowed.

• Known history of tuberculosis (TB).

• Suspicion of TB at chest X-rays at screening or within three months prior to firstadministration of study product.

• Suspicion of latent or active tuberculosis as defined by :

• Positive Mantoux/Purified Protein Derivative (PPD)test (> ou = 5mm induration measured 48 to 72 hours after intradermal injection of tuberculin) at screening or within 30days prior to first administration of study product.

• and/or positive interferon-γ (IFN γ) TB diagnostic test (as measured by the ELISpotmethod) at screening or within three months prior to first administration of studyproduct.

• Positive for HIV, HCV or HBV including HBsAg and anti-HBc antibodies.

• Use of any investigational or non-registered product (drug or vaccine).

• Administration of any live vaccine within three months prior to study entry

• Any confirmed or suspected immunosuppressive or immunodeficient condition.