Infliximab for Takayasu arteritis

Inclusion criteria

• {"criterion_text":"- \tDiagnosis of Takayasu arteritis (see protocol)"}
• {"criterion_text":"- \tFor 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."}
• {"criterion_text":"- \tActive disease according to the international criteria of the National Institute of Health (NIH) (appendix 2) - see protocol"}
• {"criterion_text":"- \tRefractory/relapsing disease or symptomatic severe arterial involvement"}
• {"criterion_text":"- \tFor Refractory/relapsing disease, patients with one immunosuppressive agent (methotrexate, azathioprine, mercaptopurine or mycophenolate mofetil, leflunomide, ciclosporine, hydroxychloroquine) with no change in dosage within the last 30 days unless allergy/intolerance or contraindication to immunosuppressive agents."}
• {"criterion_text":"- \tAge of 15 years or older"}
• {"criterion_text":"- \tWeight 40 – 120 kg"}
• {"criterion_text":"- \tFor symptomatic severe arterial involvement, patients with one immunosuppressive agent (methotrexate, azathioprine, mercaptopurine or mycophenolate mofetil, leflunomide, ciclosporine, hydroxychloroquine) unless allergy/intolerance or contraindication to immunosuppressive agents."}
• {"criterion_text":"- \tMedical follow-up in a university or general hospital in France"}
• {"criterion_text":"- \tSocial insurance"}
• {"criterion_text":"- \tWilling and able to provide written informed consent"}
• {"criterion_text":"- \tChest X-ray results (postero-anterior and lateral) or chest CT within 12 weeks prior to the inclusion & randomization visit with no evidence of active tuberculosis, active infection, or malignancy"}
• {"criterion_text":"- \tTuberculosis assessment meeting one of the following conditions (see protocol)"}
• {"criterion_text":"- \tNegative human immunodeficiency virus (HIV) serology, negative hepatitis C RNA, and hepatitis B surface antigen within 3 months."}
• {"criterion_text":"- \tWilling and able to comply with treatment and follow-up procedures required by the study protocol"}
• {"criterion_text":"- \tFor female subjects of child-bearing age, a negative serum pregnancy test and no pregnancy plans within 12 months."}

Exclusion criteria

• {"criterion_text":"- \tActive tuberculosis or latent tuberculosis infection currently treated less than 3 weeks"}
• {"criterion_text":"- \t Hepatic dysfunction as shown by aspartate transaminase (AST) or alanine transaminase (ALT) levels >5‐fold the upper limit of normal"}
• {"criterion_text":"- \tHeart failure ≥ stage III / IV NYHA,"}
• {"criterion_text":"- \tHistory 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."}
• {"criterion_text":"- \tHistory of multiple sclerosis and/or demyelinating disorder"}
• {"criterion_text":"- \tHistory of severe allergic or anaphylactic reactions to infliximab, any chimeric murine monoclonal antibody, tocilizumab, and their respective excipients or prednisone (or the prednisolone)."}
• {"criterion_text":"- \tHistory of immediate hypersensitivity reaction to iodinated and gadolinium-based contrast media"}
• {"criterion_text":"- \tCytopenia: Hemoglobin < 8.5 g/dL, absolute neutrophil < 1.5 G/L, Platelet count < 80 G/L"}
• {"criterion_text":"- \tAny live (attenuated) vaccine fewer than 4 weeks before enrolment. Recombinant or killed virus vaccines fewer than 2 weeks before the inclusion & randomization visit."}
• {"criterion_text":"- \tUse 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 3 months prior to the inclusion & randomization visit b.\tPast treatment with rituximab within the past months, or past treatment with rituximab more than months ago where the B lymphocytes count has not returned to normal at time of the inclusion & randomization visit c.\tTreatment with any systemic alkylating agents within 3 months prior to the inclusion & randomization visit (e.g., cyclophosphamide, chlorambucil)"}
• {"criterion_text":"- \tIndication to initiate infliximab or tocilizumab for another active disease than Takayasu arteritis"}
• {"criterion_text":"- \tEvidence of active infection (includes chronic infection)"}
• {"criterion_text":"- \tLack of affiliation to a social security benefit plan (as a beneficiary or assignee)"}
• {"criterion_text":"- \tPresence of any of the following on-ongoing and on-treatment disease processes: o\tMicroscopic polyangiitis o\tGranulomatosis with polyangiitis o\tEosinophilic granulomatosis with polyangiitis o\tPolyarteritis nodosa o\tCogan’s syndrome o\tBehcet’s disease o\tKawasaki’s disease o\tAtypical mycobacterial infections o\tDeep fungal infections o\tLymphoma, lymphomatoid granulomatosis, or other type of malignancy tha mimics vasculitis o\tCryoglobulinemic vasculitis o\tSystemic lupus erythematosus o\tRheumatoid arthritis o\tMixed connective tissue disease or any overlap autoimmune syndrome o\tKnown constitutive immunodeficiency"}
• {"criterion_text":"- \tInfection requiring treatment with antibiotics within 2 weeks prior to the inclusion & randomization visit"}
• {"criterion_text":"- \tInfection with positive human immunodeficiency virus (HIV) serology, positive hepatitis C RNA, or a positive hepatitis B surface antigen."}
• {"criterion_text":"- \tPregnancy or lactation"}
• {"criterion_text":"- \tInability to comply with study guidelines"}
• {"criterion_text":"- \tInability to provide informed consent"}
• {"criterion_text":"- \tAlcohol 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"}
• {"criterion_text":"- \tSevere renal insufficiency (creatinine clairance <30mL/min/1,73m2)"}

Primary endpoints

• {"endpoint_text":"- Proportion at 6 months after Day1 of treatment, of patients with prednisone (or the prednisolone) ≤ 0.1mg/kg per day and sustained inactive disease from M3 to M6 and same biological therapy from Day1 of treatment among the randomized patients in the same arm.","definition_or_measurement_approach":"Measured at 6 months after Day1; defined as the proportion of randomized patients in each arm with prednisone (or prednisolone) ≤ 0.1 mg/kg/day and sustained inactive disease from month 3 to month 6 and receiving the same biological therapy from Day1."}

Secondary endpoints

• {"endpoint_text":"- \tIncidence of relapse as defined by the NIH criteria between M3 and M6 after Day1 of treatment.","definition_or_measurement_approach":"Incidence of relapse measured between month 3 and month 6 after Day1, using NIH criteria for relapse."}
• {"endpoint_text":"- \tIncidence of traitement failure at M3 after Day1 of treatment i.e disease still active according to the NIH criteria","definition_or_measurement_approach":"Incidence of treatment failure at month 3 after Day1, defined as disease still active per NIH criteria."}
• {"endpoint_text":"- \tProportion at 6 months after Day1 of treatment of patients with prednisone (or the prednisolone) ≤ 0.1mg/kg per day and sustained inactive disease (modified NIH score (without criterion 3) ≤ 1) from M3 to M6 and same biological therapy from Day1 of treatment among the randomized patients in the same arm.","definition_or_measurement_approach":"Measured at month 6; proportion with prednisone ≤0.1 mg/kg/day and sustained inactive disease from M3 to M6 defined by modified NIH score (without criterion 3) ≤ 1, and same biological therapy since Day1."}
• {"endpoint_text":"- \tIncidence of relapse as defined by the modified NIH criteria (without criterion 3) ≥2 between M3 and M6 after Day1 of treatment.","definition_or_measurement_approach":"Incidence of relapse between M3 and M6 using modified NIH criteria (excluding criterion 3), with threshold ≥2."}
• {"endpoint_text":"- \tincidence of traitement failure at M3 after Day1 of treatment i.e disease still active according to the modified NIH criteria (without criterion 3) ≥2","definition_or_measurement_approach":"Incidence of treatment failure at M3 defined by modified NIH criteria (without criterion 3) with score ≥2."}
• {"endpoint_text":"- \tIncidence of revascularization procedures (endovascular or surgical) from Day1 of treatment to M6 and M12 after Day1 of treatment","definition_or_measurement_approach":"Incidence of endovascular or surgical revascularization procedures occurring from Day1 up to month 6 and month 12 after Day1."}
• {"endpoint_text":"- \tCumulative doses of prednisone (or the prednisolone) in each arm at M6 and M12 after Day1 of treatment","definition_or_measurement_approach":"Cumulative prednisone/prednisolone dose in each arm measured at month 6 and month 12 after Day1."}
• {"endpoint_text":"- \tIncidence of adverse events of grades III or IV at M6 and M12 after Day1 of treatment","definition_or_measurement_approach":"Incidence of grade III/IV adverse events measured at month 6 and month 12 after Day1 (grading per trial safety standards)."}
• {"endpoint_text":"- \tMean change in the quality of life questionnaire SF-36 from D1 of treatment to M6 and M12 after treatment","definition_or_measurement_approach":"Mean change in SF-36 scores from Day1 to month 6 and month 12 after treatment."}
• {"endpoint_text":"- \tProportion of new vascular lesions at M6 and M12 after Day1 of treatment assessed by angio-CT or MR angiography","definition_or_measurement_approach":"Proportion of patients with new vascular lesions at month 6 and month 12 assessed by angio-CT or MR angiography."}

France

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

531

Number Of Sites

18

Number Of Participants

50

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Ministry of Health - PHRC","duties_or_roles":"Source of monetary support","organisation_type":""}