NCT01040715

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at below P25 for phase_2 rheumatoid-arthritis

Timeline
Completed

Started Dec 2009

Longer than P75 for phase_2 rheumatoid-arthritis

Geographic Reach
7 countries

35 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2009

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

December 28, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 30, 2009

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
Last Updated

September 18, 2014

Status Verified

September 1, 2014

Enrollment Period

2.8 years

First QC Date

December 28, 2009

Last Update Submit

September 17, 2014

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritisanti-drug antibodiesRheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38

    Day 38

Secondary Outcomes (1)

  • Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline

    3 months

Study Arms (3)

TNFa Kinoid dose 1

EXPERIMENTAL
Biological: TNFa KinoidBiological: TNF kinoid

TNFa Kinoid dose 2

EXPERIMENTAL
Biological: TNFa KinoidBiological: TNF kinoid

TNFa Kinoid dose 3

EXPERIMENTAL
Biological: TNFa KinoidBiological: TNF kinoid

Interventions

TNFa KinoidBIOLOGICAL

TNFa kinoid

TNFa Kinoid dose 1TNFa Kinoid dose 2TNFa Kinoid dose 3
TNF kinoidBIOLOGICAL

IM administration 2 or 3 injections within 28 days

TNFa Kinoid dose 1TNFa Kinoid dose 2TNFa Kinoid dose 3

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 .

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

Centro especializado en Investigaciones Medicas (CEIM)

Buenos Aires, Argentina

Location

Hospital Sirio Libanes

Buenos Aires, Argentina

Location

Hospital Italiano de Cordoba

Córdoba, Argentina

Location

Centro de Investigaciones Reumatologicas

San Miguel de Tucumán, Argentina

Location

Centro Médico Privado de Reumatología

San Miguel de Tucumán, Argentina

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universiteit ZiekenHuis Katholiek Universiteit Leuven

Leuven, 3000, Belgium

Location

Universitaires Cliniques St. Luc (Mont-Godinne)

Mont-Godinne, Belgium

Location

Diagnostic and Consulting Center SV

Plovdiv, Bulgaria

Location

Military Medical Academy

Sofia, Bulgaria

Location

National Multiprofile Transport Hospital "Tzar Boris III"

Sofia, Bulgaria

Location

University Hospital for Active Treatment "Sveti Ivan Rilski"

Sofia, Bulgaria

Location

MBAL University Stara Zagora

Stara Zagora, Bulgaria

Location

Medical Center "Chaika" Ltd

Varna, Bulgaria

Location

"Sociedad Médica del Aparato Locomotor SA"

Santiago, Chile

Location

Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"

Santiago, Chile

Location

General Hospital Karlovac

Karlovac, Croatia

Location

Thalassotherapia

Opatija, Croatia

Location

KBC Split

Split, Croatia

Location

Clinical Hospital "Sveti Duh"

Zagreb, Croatia

Location

University Hospital Sisters of Mercy

Zagreb, Croatia

Location

CHU Avicenne

Bobigny, 93000, France

Location

Hopital Pellegrin

Bordeaux, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, 92100, France

Location

Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802

Le Kremlin-Bicêtre, 94275, France

Location

C.H.U. Hôpital Roger Salengro

Lille, 59037, France

Location

Hôpital Lapeyronie

Montpellier, 34295, France

Location

Hôpital Xavier Bichat

Paris, 75018, France

Location

Hopital La Pitie Salpetriere

Paris, France

Location

Hopital Lariboisière

Paris, France

Location

CHU Strasbourg-Hautepierre

Strasbourg, 67098, France

Location

"Dr. Constantin Opris" Emergency County Hospital Baia Mare

Baia Mare, Romania

Location

"Dr. I Cantacuzino" Clinical Hospital

Bucharest, Romania

Location

Ianuli Med Consult SRL

Bucharest, Romania

Location

Rehabilitation Clinical Hospital Iasi

Iași, Romania

Location

Related Publications (1)

  • 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.

    PMID: 25517733DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Patrick Durez, MD

    Cliniques Universitaires St Luc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 28, 2009

First Posted

December 30, 2009

Study Start

December 1, 2009

Primary Completion

October 1, 2012

Study Completion

September 1, 2013

Last Updated

September 18, 2014

Record last verified: 2014-09

Locations

BE(3)BU(6)CR(5)FR(10)AR(5)CL(2)RO(4)