2024-511906-21-00招募中3 期
Efficacy of Tocilizumab in association to steroids in giant cell arteritis with cerebro-vascular involvement patients (ToGiAS). A french prospective multicentre randomized versus placebo phase III trial (TOGIAC)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 7
- 主要终点
- The primary endpoint is composite: complete remission of GCA with cerebrovascular involvement (clinical, biological, and PET uptake) including absence of clinical and MRI ischemic stroke recurrence at 24 weeks
研究概览
简要总结
Assess the efficacy of tocilizumab to induce complete remission of GCA with cerebrovascular involvement (clinical, radiological) and absence of clinical and MRI ischemic stroke recurrence at 24 weeks.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age > 60 years
- •Diagnosis of : - GCA (according to ACR criteria or positive temporal artery biopsy) (de novo and/or relapse) - And neurovascular involvement: Defined by PET uptake of vertebral and/or carotid arteries (extra or intra cranial) or angioCT/MRI showing arterial involvement inconsistent with atherosclerosis Either Ischemic stroke (including TIA) in the vertebro-basilar or carotid territory (symptomatic arterial involvement) Without Ischemic stroke (including TIA) (asymptomatic arterial involvement)
- •Inclusion should be done within 4 weeks after the stroke concerning the “symptomatic” patients within 4 weeks after the diagnosis of GCA (or relapse) concerning the patients with asymptomatic neurovascular involvement. Within 21 days after starting the corticosteroids
- •Signed Informed Consent Form
- •Affiliation to social security
排除标准
- •Other proven cause of stroke: atrial fibrillation, significant atheromatous stenosis of carotid or vertebro-basilar arteries
- •Previous treatment with tofacitinib within 2 months before the baseline
- •Treatment with cyclophosphamide within 24 weeks of baseline
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone
- •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal disease
- •Current liver disease, as determined by the investigator
- •History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations
- •Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds)
- •Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- •Active TB requiring treatment within the previous 3 years (Patients treated for TB with no recurrence within 3 years and patients treated for latent TB within 3 years were eligible)
- •Primary or secondary immunodeficiency (history of or currently active)
- •Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever was longer) of screening
- •Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that had been excised and cured)
- •History of alcohol, drug, or chemical abuse within 1 year prior to screening
- •Body weight >150 kg
- •Serum creatinine >1.4 mg/dL (124 µmol/L) in female patients and 1.6 mg/dL (141 µmol/L) in male patients
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)× 3 Upper limit of normal (ULN)>
- •Platelet count < 100 109/L (100,000/mm3)
- •Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- •White blood cells <3.0 x109/L (3000/mm3)
- •Absolute neutrophil count < 2.0 x 109/L (2000/mm3)
- •Absolute lymphocyte count < 0.5 X 109/L (500/mm3)
- •Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20 within 6 months before the baseline
- •Positive hepatitis B surface antigen or hepatitis C antibody
- •Contraindication to aspirin, clopidogrel, steroids use, rifampicin and/or izoniazid
- •Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization, except arterial thrombectomy if necessary for ischemic stroke
- •Transplanted organs (except corneal transplant performed more than 3 months prior to screening)
- •Inability to provide informed consent
- •Participation in another interventional research
- •Treatment with IV gamma globulin or plasmapheresis within 24 weeks of baseline
- •Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation within 2 months before the baseline
- •Previous treatment with tocilizumab (TCZ) within 6 months before the baseline
- •Immunization with a live/attenuated vaccine within 4 weeks prior to baseline or simultaneously with tocilizumab treatment
- •Treatment with hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil (MMF) within 4 weeks of baseline
- •Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
结局指标
主要结局
The primary endpoint is composite: complete remission of GCA with cerebrovascular involvement (clinical, biological, and PET uptake) including absence of clinical and MRI ischemic stroke recurrence at 24 weeks
The primary endpoint is composite: complete remission of GCA with cerebrovascular involvement (clinical, biological, and PET uptake) including absence of clinical and MRI ischemic stroke recurrence at 24 weeks
次要结局
- Relapse-free survival will be assessed at weeks 4, 12, 24 and 52
- Time to remission will be assessed at weeks 4, 12, 24 and 52
- Serious adverse event-free survival will be assessed at weeks 4, 12, 24 and 52
- Neurovascular imaging improvement: angio-CT improvement of vasculitis lesions and /or improvement or disappearance of PET FDG uptake will be assessed at weeks 4, 12, 24 and 52
- Number and percentages of deaths Relapse-free survival will be assessed at weeks 4, 12, 24 and 52
- Number and percentages of patients with rankin score 0-1 Relapse-free survival will be assessed at weeks 4, 12, 24 and 52
- Percentage of clinical and MRI ischemic stroke recurrence at 24 weeks
- Influence of tocilizumab treatment on cumulative steroid dose at 24 weeks
- Safety of tocilizumab assessed by adverse events (mostly nasopharyngitis, headache, hypertension, injection site reactions and serious adverse events (mostly upper respiratory tract infections, but also rare liver damage), neutropenia and hypercholesterolemia
研究者
Coordinating investigator
Scientific
Assistance Publique Hopitaux De Paris
研究点 (7)
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