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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Sirio 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
        • Hôpital Lariboisière
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Neovacs

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 28, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 30, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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