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Takayasu ArteritisPhase 2INTOReTAKNCT04564001

Multicentre, Randomized, Prospective Trial Evaluating the Efficacy and Safety of Infliximab to Tocilizumab in Refractory or Relapsing Takayasu Arteritis

A Phase 2 study testing Infliximab and Tocilizumab in people with Takayasu Arteritis, run by Assistance Publique - Hôpitaux de Paris.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Takayasu arteritis (TA) is a vasculitis of unknown origin, resulting in progressive thickening and stenosis of large and medium arteries (the aorta and its major branches, and the pulmonary arteries). First line therapy of TA consists of high dose corticosteroids (CS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Takayasu Arteritis
What is being tested?
Infliximab and Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
No sites listed yet
Study dates
Sep 2020to Sep 2023
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of Takayasu disease according to the international criteria of the American College of Rheumatology (ACR)
  • Age at disease onset < 40 years
  • Claudication of extremities
  • Decreased brachial artery pulse (one or both arteries)
  • Blood pressure difference of >10mm Hg between the arms
  • Bruit over subclavian arteries or aorta
Show all 31Show fewer
  • Active disease according to the international criteria of the National Institute of Health (NIH)
  • New onset or worsening of at least two of the following four criteria
  • Systemic features
  • Elevated erythrocyte sedimentation rate
  • Features of vascular ischemia or inflammation
  • Typical angiographic features
  • Refractory/relapsing disease
  • Failure of disease to respond to daily corticosteroids therapy (1mg/kg/day for > 1month), i.e. disease still active
  • Inability to taper corticosteroids below 10mg/day within 6 months
  • Inability to discontinue corticosteroids after 1 year of treatment
  • Relapse of disease after gradual decrease of corticosteroids therapy
  • Patients with one immunosuppressive agent (methotrexate, azathioprine, mercaptopurine or mycophenolate mofetil)
  • Age of 18 years or older
  • Weight 40 - 120 kg
  • Medical follow-up in a university or general hospital in France
  • Social insurance
  • Willing and able to provide written informed consent
  • Willing and able to comply with treatment and follow-up procedures required by the study protocol
  • For female subjects of child-bearing age, a negative serum pregnancy test and no pregnancy plans within 12 months
  • For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, or condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.
  • Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to enrollment with no evidence of active tuberculosis, active infection, or malignancy
  • Tuberculosis assessment:
  • Active Tuberculosis infection treatment achieved
  • Completion of at least 3 weeks treatment for Latent Tuberculosis infection
  • Negative tuberculin skin test (TST) or interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test)

Who cannot join

  • Active tuberculosis or untreated latent tuberculosis
  • Evidence of active infection (includes chronic infection)
  • Infection requiring treatment with antibiotics within 2 weeks prior to enrollment
  • Infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen.
  • Pregnancy or lactation
  • Inability to comply with study guidelines
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  • Inability to provide informed consent
  • Immunosuppressant type or dose modification within 30 days prior to enrollment
  • Alcohol or drug abuse, that, in the investigator's opinion, could prevent a subject from fulfilling the study requirements or that would increase the risk of study procedures
  • Severe renal insufficiency (creatinine clairance <30mL/min/1,73m2)
  • Hepatic dysfunction as shown by aspartate transaminase (AST) or alanine transaminase (ALT) levels >5-fold the upper limit of normal
  • Heart failure ≥ stage III / IV NYHA,
  • History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin, or solid tumors treated with curative therapy and disease free for at least 5 years.
  • History of multiple sclerosis and/or demyelinating disorder
  • History of severe allergic or anaphylactic reactions to infliximab, any chimeric murine monoclonal antibody, tocilizumab, and their respective excipients or prednisone
  • History of immediate hypersensitivity reaction to iodinated and gadolinium-based contrast media
  • Cytopenia: Hemoglobin < 8.5 g/dL, absolute neutrophil < 1.5 G/L, Platelet count < 80 G/L
  • Any live (attenuated) vaccine fewer than 4 weeks before enrolment. Recombinant or killed virus vaccines fewer than 2 weeks before enrolment.
  • Use of the following systemic treatments during the specified periods
  • Treatment with biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, anakinra, tocilizumab, etanercept, abatacept, ixekizumab, secukinumab, ustekinumab, alemtuzumab) within 6 months prior to enrollment
  • Past treatment with rituximab within the past 12 months, or past treatment with rituximab more than 12 months ago where the B lymphocytes count has not returned to normal at time of enrollment
  • Treatment with any systemic alkylating agents within 6 months prior to enrollment (e.g., cyclophosphamide, chlorambucil)
  • Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
  • Presence of any of the following disease processes:
  • Microscopic polyangiitis
  • Granulomatosis with polyangiitis
  • Eosinophilic granulomatosis with polyangiitis
  • Polyarteritis nodosa
  • Cogan's syndrome
  • Behcet's disease
  • Sarcoidosis
  • Kawasaki's disease
  • Atypical mycobacterial infections
  • Deep fungal infections
  • Lymphoma, lymphomatoid granulomatosis, or other type of malignancy tha mimics vasculitis
  • Cryoglobulinemic vasculitis
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Mixed connective tissue disease or any overlap autoimmune syndrome
  • Known constitutive immunodeficiency

Trial locations and contacts

No sites are listed yet.

Tristan MIRAULT contact

+33156093051

tristan.mirault@aphp.fr

Matthieu Resche-Rigon contact

+33142499742

matthieu.resche-rigon@univ-paris-diderot.fr

About this study

Takayasu arteritis (TA) is a vasculitis of unknown origin, resulting in progressive thickening and stenosis of large and medium arteries (the aorta and its major branches, and the pulmonary arteries). First line therapy of TA consists of high dose corticosteroids (CS). Between 20 and 50% of cases respond to CS alone, with subsequent resolution of symptoms and stabilization of vascular abnormalities. Although second-line agents (methotrexate, azathioprine, mercaptopurine, mycophenolate mofetil) may result in initial remission, relapses remain common when prednisone is tapered. Thus, 50% of CS-resistant or relapsing TA patients may achieve sustained remission with the addition of methotrexate. During the last decade, biologics such as anti-tumor necrosis factor alpha (anti-TNFα) and anti-interleukin-6 (anti-IL-6) have been used as third-line treatment in refractory or relapsing TA. Almost 90% of CS-methotrexate resistant TA cases responded to infliximab, an anti-TNFα, and sustained remission was obtained in 37 to 76% of the cases. Tocilizumab, an anti-IL-6 has given similar results with 68% of sustained remission in refractory TA. Irrespective of classical cardiovascular risk factors, the systemic inflammation and CS use play a pivotal role in the occurrence of cardiovascular thrombotic events (CVEs). As CVEs overlap with TA complications it is primordial to drastically taper CS in that vasculitis. We therefore hypothesize that Infliximab or Tocilizumab can achieve a remission in more than 70% of refractory/relapsing TA cases to CS associated to a second-line agent. INTOReTAK, first randomized prospective study in TA, has an original design testing Infliximab and Tocilizumab propensity to achieve over 70% of sustained remission in refractory/relapsing TA and evaluating jointly the 2 arms. The primary objective of this study is to obtain, by arm, ≥ 70% of patients at 6 months after randomization with prednisone ≤ 0.1mg/kg per day and inactive disease (NIH score ≤ 1) during the last 3 months.

Being tested
Infliximab, Tocilizumab
Medical subject headings
Takayasu Arteritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfliximabDrug

    Patients will receive infliximab 5mg/kg intravenously at week 0; 2; 6; 14; 22 in arm A

  • TocilizumabDrug

    Patients will receive tocilizumab 8mg/kg intravenously at week 0; 4; 8; 12; 16; 20; 24 in arm B

Study groups in NCT04564001
Study groupRoleWhat they receive
A ( Infliximab)ExperimentalInfliximab 5mg/kg intravenously at week 0; 2; 6; 14; 22 following prescription recommendations
Receives: Drug: Infliximab
B (Tocilizumab)ExperimentalTocilizumab : 8mg/kg intravenously at week 0; 4; 8; 12; 16; 20; 24 following prescription recommendations
Receives: Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients with prednisone ≤ 0.1mg/kg per day and sustained inactive disease (NIH score ≤ 1) from M3 to M6 and same biological therapy from randomization

    Measured: at 6 months after randomization

Secondary outcomes (12)

  1. Incidence of relapse as defined by the NIH criteria

    Measured: between 3 and 6 months

  2. Incidence of traitement failure

    Traitment failure will be defined as disease still active according to the NIH criteria

    Measured: at 3 months after randomization

  3. Incidence of revascularization procedures

    Measured: at 6 months after randomization

  4. Incidence of revascularization procedures

    Measured: at 12 months after randomization

  5. Cumulative doses of prednisone

    Measured: at 6 months after randomization

  6. Cumulative doses of prednisone

    Measured: at 12 months after randomization

  7. Incidence of adverse events of grades III and IV

    Measured: at 6 months after randomization

  8. Incidence of adverse events of grades III and IV

    Measured: at 12 months after randomization

  9. Quality of life will be assessed using the SF36 questionnaire

    Measured: at 6 months

  10. Quality of life

    Quality of life will be assessed using the SF36 questionnaire

    Measured: at 12 months

  11. Proportion of new vascular lesions

    Measured: at 6 months

  12. Proportion of new vascular lesions

    Measured: at 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2020
  2. Study startSep 2020 (estimated)
  3. Primary completionFeb 2021 (estimated)
  4. Study completionSep 2023 (estimated)

Resources

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
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04564001
Sponsor's protocol ID
P160909
Acronym
INTOReTAK
Status last verified
Sep 2020
First submitted
21 Sep 2020
Last updated
25 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Infliximab and Tocilizumab in people with Takayasu Arteritis, run by Assistance Publique - Hôpitaux de Paris.

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 31 inclusion and 40 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: status not confirmed, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Tristan MIRAULT (+33156093051, tristan.mirault@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with prednisone ≤ 0.1mg/kg per day and sustained inactive disease (NIH score ≤ 1) from M3 to M6 and same biological therapy from randomization (time frame: at 6 months after randomization). 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 NCT04564001.

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 25 Sep 2020.

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