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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01040715
• Other study ID #: TNF-K-003
• Secondary ID: 2009-012041-35
• Status: Completed
• Phase: Phase 2
• First received: December 28, 2009
• Last updated: September 17, 2014
• Start date: December 2009
• Est. completion date: September 2013

Study information

• Verified date: September 2014
• Source: Neovacs
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Switzerland: SwissmedicBulgaria: Bulgarian Drug AgencyArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCroatia: Agency for Medicinal Product and Medical DevicesRomania: National Medicines AgencyChile: Comisión Nacional de Investigación Científica y Tecnológica
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 TNFa antagonist treatment.

• Secondary treatment failure to maximum one previous TNFa 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 TNFa 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 TNFa 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-? (IFN ?) 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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• TNFa Kinoid
TNFa kinoid
• TNF kinoid
IM administration 2 or 3 injections within 28 days

Locations

Country	Name	City	State
Argentina	Centro especializado en Investigaciones Medicas (CEIM)	Buenos Aires
Argentina	Hospital Sirio Libanes	Buenos Aires
Argentina	Hospital Italiano de Cordoba	Cordoba
Argentina	Centro de Investigaciones Reumatologicas	San Miguel de Tucumán
Argentina	Centro Médico Privado de Reumatología	San Miguel de Tucumán
Belgium	Cliniques Universitaires Saint Luc	Brussels
Belgium	Universiteit ZiekenHuis Katholiek Universiteit Leuven	Leuven
Belgium	Universitaires Cliniques St. Luc (Mont-Godinne)	Mont-Godinne
Bulgaria	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
Chile	"Sociedad Médica del Aparato Locomotor SA"	Santiago de Chile
Chile	Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"	Santiago de Chile
Croatia	General Hospital Karlovac	Karlovac
Croatia	Thalassotherapia	Opatija
Croatia	KBC Split	Split
Croatia	Clinical Hospital "Sveti Duh"	Zagreb
Croatia	University Hospital Sisters of Mercy	Zagreb
France	CHU Avicenne	Bobigny
France	Hopital Pellegrin	Bordeaux
France	Hôpital Ambroise Paré	Boulogne Billancourt
France	Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802	Le Kremlin Bicêtre
France	C.H.U. Hôpital Roger Salengro	Lille
France	Hôpital Lapeyronie	Montpellier
France	Hopital La Pitie Salpetriere	Paris
France	Hopital Lariboisière	Paris
France	Hôpital Xavier Bichat	Paris
France	CHU Strasbourg-Hautepierre	Strasbourg
Romania	"Dr. Constantin Opris" Emergency County Hospital Baia Mare	Baia Mare
Romania	"Dr. I Cantacuzino" Clinical Hospital	Bucharest
Romania	Ianuli Med Consult SRL	Bucharest
Romania	Rehabilitation Clinical Hospital Iasi	Iasi

Sponsors (1)

Lead Sponsor	Collaborator
Neovacs

Countries where clinical trial is conducted

Argentina,  Belgium,  Bulgaria,  Chile,  Croatia,  France,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38		Day 38	No
Secondary	Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline		3 months	No