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

September 17, 2014 updated by: Neovacs

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Centro especializado en Investigaciones Medicas (CEIM)
      • Buenos Aires, Argentina
        • Hospital Sírio Libanês
      • Cordoba, Argentina
        • Hospital Italiano de Córdoba
      • San Miguel de Tucumán, Argentina
        • Centro de Investigaciones Reumatológicas
      • San Miguel de Tucumán, Argentina
        • Centro Medico Privado de Reumatologia
  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint Luc
      • Leuven, Belgium, 3000
        • Universiteit ZiekenHuis Katholiek Universiteit Leuven
      • Mont-Godinne, Belgium
        • Universitaires Cliniques St. Luc (Mont-Godinne)
  • Bulgaria
      • Plovdiv, Bulgaria
        • Diagnostic and Consulting Center SV
      • Sofia, Bulgaria
        • Military Medical Academy
      • Sofia, Bulgaria
        • National Multiprofile Transport Hospital "Tzar Boris III"
      • Sofia, Bulgaria
        • University Hospital for Active Treatment "Sveti Ivan Rilski"
      • Stara Zagora, Bulgaria
        • MBAL University Stara Zagora
      • Varna, Bulgaria
        • Medical Center "Chaika" Ltd
  • Chile
      • Santiago de Chile, Chile
        • "Sociedad Médica del Aparato Locomotor SA"
      • Santiago de Chile, Chile
        • Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"
  • Croatia
      • Karlovac, Croatia
        • General Hospital Karlovac
      • Opatija, Croatia
        • Thalassotherapia
      • Split, Croatia
        • KBC Split
      • Zagreb, Croatia
        • Clinical Hospital "Sveti Duh"
      • Zagreb, Croatia
        • University Hospital Sisters of Mercy
  • France
      • Bobigny, France, 93000
        • CHU Avicenne
      • Bordeaux, France
        • Hôpital Pellegrin
      • Boulogne Billancourt, France, 92100
        • Hôpital Ambroise Paré
      • Le Kremlin Bicêtre, France, 94275
        • Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802
      • Lille, France, 59037
        • C.H.U. Hôpital Roger Salengro
      • Montpellier, France, 34295
        • Hopital Lapeyronie
      • Paris, France
        • Hopital Lariboisiere
      • Paris, France
        • Hôpital La Pitié Salpêtrière
      • Paris, France, 75018
        • Hôpital Xavier Bichat
      • Strasbourg, France, 67098
        • CHU Strasbourg-Hautepierre
  • Romania
      • Baia Mare, Romania
        • "Dr. Constantin Opris" Emergency County Hospital Baia Mare
      • Bucharest, Romania
        • "Dr. I Cantacuzino" Clinical Hospital
      • Bucharest, Romania
        • Ianuli Med Consult SRL
      • Iasi, Romania
        • Rehabilitation Clinical Hospital Iasi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38
Time Frame: Day 38
Day 38

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neovacs

Investigators

  • Principal Investigator: Patrick Durez, MD, Cliniques Universitaires St Luc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

December 28, 2009

First Submitted That Met QC Criteria

December 29, 2009

First Posted (Estimate)

December 30, 2009

Study Record Updates

Last Update Posted (Estimate)

September 18, 2014

Last Update Submitted That Met QC Criteria

September 17, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TNF-K-003
  • 2009-012041-35 (Registry Identifier: EMEA)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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