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

A Phase II, Randomized, Double-blind, Controlled Study to Evaluate the Immune Responses, Safety and Clinical Efficacy of Three Doses of Neovacs' TNF-Kinoid in Adult Patients With Rheumatoid Arthritis Who Have Relapsed Despite Anti-TNFα Biological Therapy

The objective of this trial is to demonstrate that active immunization with anti-TNFα kinoid (TNF-K) is able to induce polyclonal anti-TNFα antibodies in RA patients who were previously treated with anti-TNFα mAb but have lost susceptibility to therapy.

Inclusion Criteria:

• Diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) (Arnett 1988) since at least six months prior to first study product 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 ten weeks since the last administration of certolizumab or golimumab; at least eigth weeks since the last administration of infliximab; at least four weeks since the last administration of adalimumab or etanercept
• History of positive response defined as an ACR20 or DAS 28 decrease ≥ 1.2 or by the investigator opinion with previous TNFα antagonist treatment.
• Secondary treatment failure to maximum one previous TNFα antagonist treatment as defined 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 product administration. 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 antagonists at any time prior to first study product administration.
• Administration of high doses of intra-articular corticosteroids for the treatment of an acute mono-arthritis (eg knee) within 3 months prior to first study product administration. High dose of corticosteroids is defined as > 50 mg triamcinolone or equivalent.
• History of documented severe bacterial infection within 28 days prior to first immunization
• 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 they are administered at stable dosage since at lesat 4 weeks prior to the first immunization. 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 first administration 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 30 days prior to first administration of study product.
• and/or positive interferon-γ (IFN γ) TB diagnostic test (as measured by the ELISpot method) at screening or within three months prior to first administration of study product.
• 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.