Clinical trial NCT01040715: Immunogenicity and Safety of TNFa Kinoid in Rheumatoid Arthritis With Secondary Resistance to TNFa Antagonists
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
anti-drug antibodies
Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies
Lead sponsor: Neovacs
Sponsor class: INDUSTRY
First posted: 2009-12-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38
timeFrame: Day 38
Secondary outcomes:
measure: Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline
timeFrame: 3 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Centro especializado en Investigaciones Medicas (CEIM)
city: Buenos Aires
country: Argentina
facility: Hospital Sirio Libanes
city: Cordoba
country: Argentina
facility: Hospital Italiano de Cordoba
city: San Miguel de Tucumán
country: Argentina
facility: Centro de Investigaciones Reumatologicas
city: San Miguel de Tucumán
country: Argentina
facility: Centro Médico Privado de Reumatología
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Leuven
country: Belgium
facility: Universiteit ZiekenHuis Katholiek Universiteit Leuven
city: Mont-Godinne
country: Belgium
facility: Universitaires Cliniques St. Luc (Mont-Godinne)
city: Plovdiv
country: Bulgaria
facility: Diagnostic and Consulting Center SV
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Sofia
country: Bulgaria
facility: National Multiprofile Transport Hospital "Tzar Boris III"
city: Sofia
country: Bulgaria
facility: University Hospital for Active Treatment "Sveti Ivan Rilski"
city: Stara Zagora
country: Bulgaria
facility: MBAL University Stara Zagora
city: Varna
country: Bulgaria
facility: Medical Center "Chaika" Ltd
city: Santiago de Chile
country: Chile
facility: "Sociedad Médica del Aparato Locomotor SA"
city: Santiago de Chile
country: Chile
facility: Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"
city: Karlovac
country: Croatia
facility: General Hospital Karlovac
city: Opatija
country: Croatia
facility: Thalassotherapia
city: Split
country: Croatia
facility: KBC Split
city: Zagreb
country: Croatia
facility: Clinical Hospital "Sveti Duh"
city: Zagreb
country: Croatia
facility: University Hospital Sisters of Mercy
city: Bobigny
country: France
facility: CHU Avicenne
city: Bordeaux
country: France
facility: Hopital Pellegrin
city: Boulogne Billancourt
country: France
facility: Hôpital Ambroise Paré
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802
city: Lille
country: France
facility: C.H.U. Hôpital Roger Salengro
city: Montpellier
country: France
facility: Hôpital Lapeyronie
city: Paris
country: France
facility: Hôpital Xavier Bichat
city: Paris
country: France
facility: Hopital La Pitie Salpetriere
city: Paris
country: France
facility: Hopital Lariboisière
city: Strasbourg
country: France
facility: CHU Strasbourg-Hautepierre
city: Baia Mare
country: Romania
facility: "Dr. Constantin Opris" Emergency County Hospital Baia Mare
city: Bucharest
country: Romania
facility: "Dr. I Cantacuzino" Clinical Hospital
city: Bucharest
country: Romania
facility: Ianuli Med Consult SRL
city: Iasi
country: Romania
facility: Rehabilitation Clinical Hospital Iasi
Study officials:
affiliation: Cliniques Universitaires St Luc
name: Patrick Durez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.