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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 70 YearsSexo: ALL

Criterios de inclusión

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 .

Criterios de exclusión

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.

Ubicaciones

Centro especializado en Investigaciones Medicas (CEIM)

Buenos Aires, Argentina

Hospital Sirio Libanes

Buenos Aires, Argentina

Hospital Italiano de Cordoba

Córdoba, Argentina

Centro de Investigaciones Reumatologicas

San Miguel de Tucumán, Argentina

Centro Médico Privado de Reumatología

San Miguel de Tucumán, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

TNFa Kinoid

TNF kinoid