Rheumatoid ArthritisPhase 2NCT01040715
Immunogenicity and Safety of TNFa Kinoid in Rheumatoid Arthritis With Secondary Resistance to TNFa Antagonists
A Phase 2 study testing TNFa Kinoid and TNF kinoid in people with Rheumatoid Arthritis, run by Neovacs at 35 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- TNFa Kinoid and TNF kinoid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 35 sitesin 7 countries
- Study dates
- Dec 2009to Sep 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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 .
Who cannot join
- 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.
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- 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.
Trial locations and contacts
35 sites in 7 countries.
35 sites in 7 countries
France10 sites
CHU Avicenne
Bobigny, 93000
Hopital Pellegrin
Bordeaux
Hôpital Ambroise Paré
Boulogne-Billancourt, 92100
Hôpital Bicêtre, Université Paris-Sud 11, INSERM U802
Le Kremlin-Bicêtre, 94275
C.H.U. Hôpital Roger Salengro
Lille, 59037
Hôpital Lapeyronie
Montpellier, 34295
Hôpital Xavier Bichat
Paris, 75018
Hopital La Pitie Salpetriere
Paris
Hopital Lariboisière
Paris
CHU Strasbourg-Hautepierre
Strasbourg, 67098
Bulgaria6 sites
Diagnostic and Consulting Center SV
Plovdiv
Military Medical Academy
Sofia
National Multiprofile Transport Hospital "Tzar Boris III"
Sofia
University Hospital for Active Treatment "Sveti Ivan Rilski"
Sofia
MBAL University Stara Zagora
Stara Zagora
Medical Center "Chaika" Ltd
Varna
Argentina5 sites
Centro especializado en Investigaciones Medicas (CEIM)
Buenos Aires
Hospital Sirio Libanes
Buenos Aires
Hospital Italiano de Cordoba
Córdoba
Centro de Investigaciones Reumatologicas
San Miguel de Tucumán
Centro Médico Privado de Reumatología
San Miguel de Tucumán
Croatia5 sites
General Hospital Karlovac
Karlovac
Thalassotherapia
Opatija
KBC Split
Split
Clinical Hospital "Sveti Duh"
Zagreb
University Hospital Sisters of Mercy
Zagreb
Romania4 sites
"Dr. Constantin Opris" Emergency County Hospital Baia Mare
Baia Mare
"Dr. I Cantacuzino" Clinical Hospital
Bucharest
Ianuli Med Consult SRL
Bucharest
Rehabilitation Clinical Hospital Iasi
Iași
Belgium3 sites
Cliniques Universitaires Saint Luc
Brussels, 1200
Universiteit ZiekenHuis Katholiek Universiteit Leuven
Leuven, 3000
Universitaires Cliniques St. Luc (Mont-Godinne)
Mont-Godinne
Chile2 sites
"Sociedad Médica del Aparato Locomotor SA"
Santiago
Centro de Estudios Reumatológicos- Estudios Clínicos Limitada"
Santiago
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- TNFa Kinoid, TNF kinoid
- Keywords
- Rheumatoid arthritis, anti-drug antibodies, Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNFa KinoidBiological
TNFa kinoid
TNF kinoidBiological
IM administration 2 or 3 injections within 28 days
| Study group | Role | What they receive |
|---|---|---|
| TNFa Kinoid dose 1 | Experimental | Not described Receives: Biological: TNFa Kinoid; Biological: TNF kinoid |
| TNFa Kinoid dose 2 | Experimental | Not described Receives: Biological: TNFa Kinoid; Biological: TNF kinoid |
| TNFa Kinoid dose 3 | Experimental | Not described Receives: Biological: TNFa Kinoid; Biological: TNF kinoid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38
Measured: Day 38
Secondary outcomes (1)
Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionOct 2012
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neovacs
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick Durez, MD, Principal investigator, Cliniques Universitaires St Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01040715
- Sponsor's protocol ID
- TNF-K-003
- Other IDs
- 2009-012041-35, 2009
- Status last verified
- Sep 2014
- First submitted
- 28 Dec 2009
- Last updated
- 18 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25517733
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01040715
- Acronym / sponsor ID
- TNF-K-003
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, anti-drug antibodies, Rheumatoid arthritis with secondary loss of efficacy to anti-TNFa antagonists and anti-drug antibodies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- NeovacsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 30 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TNFa Kinoid dose 1 | Experimental | Biological: TNFa Kinoid, Biological: TNF kinoid |
| TNFa Kinoid dose 2 | Experimental | Biological: TNFa Kinoid, Biological: TNF kinoid |
| TNFa Kinoid dose 3 | Experimental | Biological: TNFa Kinoid, Biological: TNF kinoid |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNFa KinoidTNFa kinoid | Biological | TNFa Kinoid dose 1, TNFa Kinoid dose 2, TNFa Kinoid dose 3 |
| TNF kinoidIM administration 2 or 3 injections within 28 days | Biological | TNFa Kinoid dose 1, TNFa Kinoid dose 2, TNFa Kinoid dose 3 |
Primary outcome
Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38
Time frame: Day 38
1 secondary outcome
Proportion of patients with a decrease of at least 1.2 in DAS28 at month 3 vs baseline
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2014.
- Derived from this study: PubMed 25517733Durez 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Durez, MD principal investigator
Cliniques Universitaires St Luc
35 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TNFa Kinoid and TNF kinoid in people with Rheumatoid Arthritis, run by Neovacs at 35 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in France, Bulgaria, Argentina, Croatia, Romania and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with at least a 3-fold increase in antibody response to TNFa vs baseline at day 38 (time frame: Day 38). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01040715, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2014.