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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: TNFa Kinoid
* Biological: TNF kinoid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNFa Kinoid dose 1<br> | Biological: TNFa Kinoid<br>* TNFa kinoid<br>Biological: TNF kinoid<br>* IM administration 2 or 3 injections within 28 days<br>|
| Experimental: TNFa Kinoid dose 2<br> | Biological: TNFa Kinoid<br>* TNFa kinoid<br>Biological: TNF kinoid<br>* IM administration 2 or 3 injections within 28 days<br>|
| Experimental: TNFa Kinoid dose 3<br> | Biological: TNFa Kinoid<br>* TNFa kinoid<br>Biological: TNF kinoid<br>* IM administration 2 or 3 injections within 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, anti-drug antibodies, Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies