INTOReTAK : INfliximab and TOcilizumab in Refractory/relapsing TAKayasu arteritis

Phase 1

• Conditions: Patients with refractory or relapsing Takayasu Arteritis desease; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

• Registration Number: EUCTR2018-003753-13-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-13
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

?Diagnosis of Takayasu disease according to the international criteria of the American College of Rheumatology (ACR) (appendix 1)
oAge at disease onset < 40 years
oClaudication of extremities
oDecreased brachial artery pulse (one or both arteries)
oBlood pressure difference of >10mm Hg between the arms
oBruit over subclavian arteries or aorta
?Active disease according to the international criteria of the National Institute of Health (NIH) (appendix 2)
New onset or worsening of at least two of the following four criteria
oSystemic features
oElevated erythrocyte sedimentation rate
oFeatures of vascular ischemia or inflammation
oTypical angiographic features
?Refractory/relapsing disease
oFailure of disease to respond to daily corticosteroids therapy (1mg/kg/day for > 1month), i.e. disease still active
oInability to taper corticosteroids below 10mg/day within 6 months
oInability to discontinue corticosteroids after 1 year of treatment
oRelapse 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
?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:
oActive Tuberculosis infection treatment achieved
oCompletion of at least 3 weeks treatment for Latent Tuberculosis infection
oNegative tuberculin skin test (TST) or interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test)
A potential subject with a positive TST or IGRA at inclusion is eligible if her/his chest X-ray does not show evidence suggestive of active tuberculosis infection and there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis infection. These subjects with a latent tuberculosis infection who have not already received a prophylactic tuberculosis treatment must agree in advance to complete such a treatment course.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

?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
?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 cyclophosphamide, interferon or infliximab and 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
a-Treatment with biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, anakinra, tocilizumab, etanercept, abatacept, ixekizumab, secukinumab, ustekinumab, alemtuzumab) within 6 months prior to enrollment
b-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
c-Treatment with any systemic alkylating agents within 6 months prior to enrollment (e.g., cyclophosphamide, chlorambucil)
?History of hypersensitivity to infliximab, other murine proteins, or to any of the excipients
?Hypersensitivity to Tocilizumab or to any of the excipients
?Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
?Presence of any of the following disease processes:
oMicroscopic polyangiitis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified