2024-512269-14-00招募中3 期
MEthotrexate versus TOcilizumab for treatment of GIant cell Arteritis: a multicenter, randomized, controlled trial
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 230
- 试验地点
- 34
- 主要终点
- Percentage of patients alive without relapse after initial remission or deviation from the scheduled regimen of prednisone at week 78 (W78).
研究概览
简要总结
To compare the efficacy of 52 weeks of MTX versus that of 52 weeks of TCZ for the treatment of GCA, after 78 weeks of follow-up.
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
- •Written consent
- •Affiliation to a social security system
- •Diagnosis of GCA, as defined by the revised GCA diagnosis criteria : Age ≥50 years at disease onset / AND History of erythrocyte sedimentation rate (ESR) ≥50 mm/h OR CRP≥20 mg/L (not mandatory if TAB is positive: see below) / AND At least one of the following: unequivocal cranial symptoms of GCA (new onset headache, scalp tenderness, jaw claudication, temporal artery abnormality, ischemia-related vision loss) OR unequivocal symptoms of polymyalgia rheumatica (PMR) / AND At least one of the following: Temporal artery biopsy (TAB) compatible with the diagnosis of GCA (non-necrotizing vasculitis with a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells) OR Evidence of large vessel vasculitis (aorta and/or epiaortic arteries) : (angio-CT or angio-MRI: thickened arterial wall (≥2mm for the aorta and ≥1mm for epiaortic arteries) and/or contrast-enhanced arteries in T1-weighted sequences) - (PET scan: grade 3 tracer uptake of the arterial wall (grade 3 = arterial SUVmax superior to the SUVmax of the liver))
- •Active GCA within 6 weeks before randomization. Active GCA is defined by ESR ≥30 mm/h or CRP ≥10 mg/L and at least one of the following: ≥1 unequivocal cranial symptom(s) of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) / ≥1 unequivocal symptom(s) of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness / any other feature(s) judged by the clinical investigator to be consistent with GCA or PMR flares
排除标准
- •Uncontrolled psychotic state
- •History of stem cell or organ transplantation (except corneas performed more than 3 months prior inclusion)
- •Primary or secondary immunodeficiency
- •Hypersensitivity to methotrexate or tocilizumab, one of its excipients or another human or murine monoclonal antibody
- •History of diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation
- •Patient refusing to sign methotrexate safety contract
- •Prior treatment with any of the following: Tocilizumab or methotrexate within 12 weeks before inclusion - Treatment with rituximab or other anti-CD20 agent within one year before inclusion - Treatment with cyclophosphamide within one year before inclusion - Hydroxychloroquine, cyclosporine A, dapsone, azathioprine, mycophenolate mofetil or janus kinase inhibitors within 4 weeks before inclusion - Tumor necrosis factor inhibitors within 8 weeks (infliximab) or 2 weeks (adalimumab or etanercept) before inclusion - Anakinra within 1 week before inclusion
- •Long-term systemic glucocorticoid therapy ((except dermocorticoids and inhaled corticoids) for other conditions than GCA or PMR
- •Patient with ≥3 prior glucocorticoid systematic therapies for another disease than GCA or PMR within the 6 months before inclusion
- •Long-term treatment with sulfamethoxazole/trimethoprim (Bactrim®)
- •Live vaccine administered within 30 days before inclusion
- •Patient unable to give his/her consent
- •Laboratory abnormalities, within 72h before inclusion : AST or ALT >1.5 x upper limit of normal (ULN) - total bilirubin >20 μmol/L (12 mg/L) - platelets<100 G/L - leukocytes <3 G/L - neutropenia <1.5 G/L - lymphopenia <0.5 G/L - haemoglobin <8 g/dL (not related to GCA activity) - clearance of creatinine <30 ml/min/1,73 m2 [CKD EPI 2009]
- •Laboratory abnormalities, within 12 months before inclusion : positive HBs antigen or positive HCV antibodies
- •History of viral hepatitis B or C (chronic or acute)
- •HIV infection
- •Persistent infection or severe infection requiring hospitalization or intravenous antibiotics within 30 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration)
- •Proven infection requiring oral antibiotics within 14 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration)
- •Prior history of histoplasmosis or listeriosis
- •Active tuberculosis
- •Latent tuberculosis (diagnosis based on history of non-treated contact, opacity with a diameter greater than 1 cm on chest radiography, or positive in vitro test: Quantiferon Gold® or T-Spot-TB®). NB: a history of tuberculosis for which treatment is over and was correctly precribed regarding usual recommendations is not an exclusion criteria, whatever the results of Quantiferon Gold® or T-Spot-TB® tests.
- •Unstable or poorly controlled, acute or chronic disease, not due to GCA, and which contraindicates tocilizumab or methotrexate: Recurrent infections, unstable ischemic heart disease, renal failure (creatinine clearance <30 ml/min/1,73 m2 [CKD EPI 2009]), liver failure, current liver disease, heart failure ≥ NYHA stage III/IV, respiratory failure - Neoplasia < 5 years, (except for in situ cervical cancer and skin carcinoma, except melanoma, with R0 resection)
- •Premenopausal women (menopause is defined as amenorrhea for more than 12 consecutive months)
- •Non-compliant patients
- •Weight<40 Kg or >100Kg
- •Patients under maintenance of justice, wardship or legal guardianship
- •History of intoxication (alcohol or medication) requiring hospitalization within 12 months before inclusion
- •Current chronic alcohol abuse (consumption > 20g/day)
- •Recent or incoming surgery within 12 months after inclusion
结局指标
主要结局
Percentage of patients alive without relapse after initial remission or deviation from the scheduled regimen of prednisone at week 78 (W78).
Percentage of patients alive without relapse after initial remission or deviation from the scheduled regimen of prednisone at week 78 (W78).
次要结局
- Percentage of patients alive without relapse after initial remission or deviation from the scheduled regimen of prednisone at W52 and 104
- Number of patients needed to treat to avoid 1 relapse at W52, 78 and 104, and will be calculated as 1/ absolute risk reduction, that is the difference between the relapse rate in TCZ group and the relapse rate in the MTX group.
- Percentage of patients in remission without prednisone at W52, 78, 104 and 156
- Percentage of patients in remission with prednisone ≤5 mg/day at W52, 78, 104 and 156
- Cumulative dose of prednisone at W52, 78, 104 and 156
- Quality of life measured by HAQ and SF36 at W 28, 52, 104 and 156
- Tiredness measured by FACIT-Fatigue at W28, 52, 104 and 156
- Time to relapse or deviation from the scheduled regimen of prednisone
- Frequency and type of side effects within 3 years after inclusion
- Frequency of GCrelated side effects within 3 years after inclusion
- Incremental costs between the two strategies at W52 and W78
- Marginal costs of both strategies between W52 and W78
- Percentage of Th1 (CD4+IFN-γ+), Th17 (CD4+IL-17+) and Treg (CD4+CD25highFoxP3+) cells among total CD4+ T cells and levels of expression of IL-6R and Gp130 by CD4+ T cells, measured by flow cytometry at W0, W12, W28, W52, W78 and in case of relapse (limited to 5 centers)
- Serum concentrations of IL-6, soluble IL-6R and soluble gp130 by Luminex at W0, W12, W28, W52, W78 and in case of relapse.
研究者
Chef de Projet Recherche
Scientific
Centre Hospitalier Universitaire De Dijon
研究点 (34)
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