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

Phase 2

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Biological: TNFa Kinoid; Biological: TNF kinoid

• Registration Number: NCT01040715
• Lead Sponsor: Neovacs

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2009-12-28
• Study First Submitted QC: 2009-12-29
• Study First Posted: 2009-12-30
• Primary Completion: 2012-10
• Study Completion: 2013-09
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-17
• Last Update Posted: 2014-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TNFa Kinoid dose 1	TNF kinoid	-
TNFa Kinoid dose 1	TNFa Kinoid	-
TNFa Kinoid dose 3	TNFa Kinoid	-
TNFa Kinoid dose 3	TNF kinoid	-
TNFa Kinoid dose 2	TNFa Kinoid	-
TNFa Kinoid dose 2	TNF kinoid	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline	3 months

Trial Locations

Locations (35)

Rehabilitation Clinical Hospital Iasi; 🇷🇴 Iasi, Romania

Universiteit ZiekenHuis Katholiek Universiteit Leuven; 🇧🇪 Leuven, Belgium

"Sociedad Médica del Aparato Locomotor SA"; 🇨🇱 Santiago de Chile, Chile

Universitaires Cliniques St. Luc (Mont-Godinne); 🇧🇪 Mont-Godinne, Belgium

General Hospital Karlovac; 🇭🇷 Karlovac, Croatia

Hospital Italiano de Cordoba; 🇦🇷 Cordoba, Argentina

Cliniques Universitaires Saint Luc; 🇧🇪 Brussels, Belgium

Hospital Sirio Libanes; 🇦🇷 Buenos Aires, Argentina

Medical Center "Chaika" Ltd; 🇧🇬 Varna, Bulgaria

Hôpital Ambroise Paré; 🇫🇷 Boulogne Billancourt, France

Hopital Lariboisière; 🇫🇷 Paris, France

Military Medical Academy; 🇧🇬 Sofia, Bulgaria

KBC Split; 🇭🇷 Split, Croatia

University Hospital Sisters of Mercy; 🇭🇷 Zagreb, Croatia

Hopital Pellegrin; 🇫🇷 Bordeaux, France

CHU Avicenne; 🇫🇷 Bobigny, France

C.H.U. Hôpital Roger Salengro; 🇫🇷 Lille, France

Hôpital Lapeyronie; 🇫🇷 Montpellier, France

Hôpital Xavier Bichat; 🇫🇷 Paris, France

Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802; 🇫🇷 Le Kremlin Bicêtre, France

Hopital La Pitie Salpetriere; 🇫🇷 Paris, France

CHU Strasbourg-Hautepierre; 🇫🇷 Strasbourg, France

Ianuli Med Consult SRL; 🇷🇴 Bucharest, Romania

Centro especializado en Investigaciones Medicas (CEIM); 🇦🇷 Buenos Aires, Argentina

Centro de Investigaciones Reumatologicas; 🇦🇷 San Miguel de Tucumán, Argentina

Centro Médico Privado de Reumatología; 🇦🇷 San Miguel de Tucumán, Argentina

Diagnostic and Consulting Center SV; 🇧🇬 Plovdiv, 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

Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"; 🇨🇱 Santiago de Chile, Chile

Thalassotherapia; 🇭🇷 Opatija, Croatia

Clinical Hospital "Sveti Duh"; 🇭🇷 Zagreb, Croatia

"Dr. Constantin Opris" Emergency County Hospital Baia Mare; 🇷🇴 Baia Mare, Romania

"Dr. I Cantacuzino" Clinical Hospital; 🇷🇴 Bucharest, Romania