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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neovacs
ClinicalTrials.gov Identifier:
NCT01040715
First received: December 28, 2009
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: TNFa Kinoid
Biological: TNF kinoid
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Neovacs:

Primary Outcome Measures:
  • Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38 [ Time Frame: Day 38 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: December 2009
Study Completion Date: September 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TNFa Kinoid dose 1 Biological: TNFa Kinoid
TNFa kinoid
Biological: TNF kinoid
IM administration 2 or 3 injections within 28 days
Experimental: TNFa Kinoid dose 2 Biological: TNFa Kinoid
TNFa kinoid
Biological: TNF kinoid
IM administration 2 or 3 injections within 28 days
Experimental: TNFa Kinoid dose 3 Biological: TNFa Kinoid
TNFa kinoid
Biological: TNF kinoid
IM administration 2 or 3 injections within 28 days

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040715

Locations
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, Argentina
Belgium
Cliniques Universitaires Saint Luc
Brussels, Belgium, 1200
Universiteit ZiekenHuis Katholiek Universiteit Leuven
Leuven, Belgium, 3000
Universitaires Cliniques St. Luc (Mont-Godinne)
Mont-Godinne, Belgium
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, Bulgaria
Chile
Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"
Santiago de Chile, Chile
"Sociedad Médica del Aparato Locomotor SA"
Santiago de Chile, 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, Croatia
France
CHU Avicenne
Bobigny, France, 93000
Hopital Pellegrin
Bordeaux, France
Hôpital Ambroise Paré
Boulogne Billancourt, France, 92100
Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802
Le Kremlin Bicêtre, France, 94275
C.H.U. Hôpital Roger Salengro
Lille, France, 59037
Hôpital Lapeyronie
Montpellier, France, 34295
Hopital La Pitie Salpetriere
Paris, France
Hopital Lariboisière
Paris, France
Hôpital Xavier Bichat
Paris, France, 75018
CHU Strasbourg-Hautepierre
Strasbourg, France, 67098
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, Romania
Sponsors and Collaborators
Neovacs
Investigators
Principal Investigator: Patrick Durez, MD Cliniques Universitaires St Luc
  More Information

No publications provided

Responsible Party: Neovacs
ClinicalTrials.gov Identifier: NCT01040715     History of Changes
Other Study ID Numbers: TNF-K-003, 2009-012041-35
Study First Received: December 28, 2009
Last Updated: September 17, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Bulgaria: Bulgarian Drug Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Croatia: Agency for Medicinal Product and Medical Devices
Romania: National Medicines Agency
Chile: Comisión Nacional de Investigación Científica y Tecnológica

Keywords provided by Neovacs:
Rheumatoid arthritis
anti-drug antibodies
Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on November 23, 2014