Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, anti-drug antibodies, Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies
Brief summary
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.
Interventions
BIOLOGICALTNFa Kinoid
TNFa kinoid
BIOLOGICALTNF kinoid
IM administration 2 or 3 injections within 28 days
Sponsors
Neovacs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38 | Day 38 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline | 3 months |
Countries
Argentina, Belgium, Bulgaria, Chile, Croatia, France, Romania
Outcome results
None listed