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

NCT ID: NCT01040715

Last Updated: 2014-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-09-30

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TNFa Kinoid dose 1

Group Type: EXPERIMENTAL

TNFa Kinoid

Intervention Type: BIOLOGICAL

TNFa kinoid

TNF kinoid

Intervention Type: BIOLOGICAL

IM administration 2 or 3 injections within 28 days

TNFa Kinoid dose 2

Group Type: EXPERIMENTAL

TNFa Kinoid

Intervention Type: BIOLOGICAL

TNFa kinoid

TNF kinoid

Intervention Type: BIOLOGICAL

IM administration 2 or 3 injections within 28 days

TNFa Kinoid dose 3

Group Type: EXPERIMENTAL

TNFa Kinoid

Intervention Type: BIOLOGICAL

TNFa kinoid

TNF kinoid

Intervention Type: BIOLOGICAL

IM administration 2 or 3 injections within 28 days

Interventions

TNFa Kinoid

TNFa kinoid

Intervention Type: BIOLOGICAL

TNF kinoid

IM administration 2 or 3 injections within 28 days

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neovacs

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Durez, MD

Role: PRINCIPAL_INVESTIGATOR

Cliniques Universitaires St Luc

Locations

Hôpital Ambroise Paré

Boulogne-Billancourt, , France

Ianuli Med Consult SRL

Bucharest, , Romania

Rehabilitation Clinical Hospital Iasi

Iași, , Romania

Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802

Le Kremlin-Bicêtre, , France

C.H.U. Hôpital Roger Salengro

Lille, , France

Hôpital Lapeyronie

Montpellier, , France

Hôpital Xavier Bichat

Paris, , France

Hopital La Pitie Salpetriere

Paris, , France

Hopital Lariboisière

Paris, , France

CHU Strasbourg-Hautepierre

Strasbourg, , France

"Dr. Constantin Opris" Emergency County Hospital Baia Mare

Baia Mare, , Romania

"Dr. I Cantacuzino" Clinical Hospital

Bucharest, , Romania

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

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Universiteit ZiekenHuis Katholiek Universiteit Leuven

Leuven, , Belgium

Universitaires Cliniques St. Luc (Mont-Godinne)

Mont-Godinne, , Belgium

Diagnostic and Consulting Center SV

Plovdiv, , Bulgaria

Military Medical Academy

Sofia, , Bulgaria

National Multiprofile Transport Hospital "Tzar Boris III"

Sofia, , Bulgaria

University Hospital for Active Treatment "Sveti Ivan Rilski"

Sofia, , Bulgaria

MBAL University Stara Zagora

Stara Zagora, , Bulgaria

Medical Center "Chaika" Ltd

Varna, , Bulgaria

"Sociedad Médica del Aparato Locomotor SA"

Santiago, , Chile

Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"

Santiago, , Chile

General Hospital Karlovac

Karlovac, , Croatia

Thalassotherapia

Opatija, , Croatia

KBC Split

Split, , Croatia

Clinical Hospital "Sveti Duh"

Zagreb, , Croatia

University Hospital Sisters of Mercy

Zagreb, , Croatia

CHU Avicenne

Bobigny, , France

Hopital Pellegrin

Bordeaux, , France

Countries

Argentina; Belgium; Bulgaria; Chile; Croatia; France; Romania

References

Durez P, Vandepapeliere P, Miranda P, Toncheva A, Berman A, Kehler T, Mociran E, Fautrel B, Mariette X, Dhellin O, Fanget B, Ouary S, Grouard-Vogel G, Boissier MC. Therapeutic vaccination with TNF-Kinoid in TNF antagonist-resistant rheumatoid arthritis: a phase II randomized, controlled clinical trial. PLoS One. 2014 Dec 17;9(12):e113465. doi: 10.1371/journal.pone.0113465. eCollection 2014.

Reference Type: DERIVED

PMID: 25517733 (View on PubMed)

Other Identifiers

2009-012041-35

Identifier Type: REGISTRY

Identifier Source: secondary_id

TNF-K-003

Identifier Type: -

Identifier Source: org_study_id