A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy of Methotrexate as Remission Maintenance Therapy After Remission-Induction Therapy With Tocilizumab and Glucocorticoids in Subjects With Giant Cell Arteritis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Time to relapse during the 12 months treatment period
研究概览
简要总结
The standard treatment for Giant Cell arteritis (GCA) is Glucocorticoids(GC), even if GC-related adverse events are commonly occuring. Therefore, other practises for reducing relapses and cumulative GC-doses are needed. Currently, the Interleukin-6-inhibitor tocilizumab is used in combination with GC to achieve higher remission rates and lower cumulative GC-doses. The use of tocilizumab also has some disadvantages. One is the increased susceptibility to infections. On top of that, a long-term follow-up of the phase II study by Villiger et al. showed a 55% relapse-rate after discontinuation of intravenous tocilizumab after a median of five months.
Studies have also shown that methotrexate(MTX) in combination with GC was able to prevent relapses and reduce cumulative GC doses.
The aim of the study is to evaluate whether MTX is superior to placebo to prevent relapses in subjects with GCA after Remission-Induction Therapy with Glucocorticoids and Tocilizumab. Our hypothesis is that Methotrexate can maintain remission, once stable remission has been induced by GC and Tocilizumab and will prevent the occurrence of relapses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects male or female, aged ≥18 years
- •Written informed consent of the capable subject for voluntary participation in the study.
- •Diagnosis of GCA as confirmed by the investigator fulfilment (also in retrospect) of the proposed extended 1990 classification criteria for GCA .
- •Previous treatment with glucocorticoids and tocilizumab for new or relapsing GCA
- •GCA patients who have been treated with tocilizumab and in whom discontinuation of tocilizumab therapy has been decided by the treating rheumatologist, within standard treatment at the department of rheumatology are eligible.
- •total tocilizumab therapy should have been at least 6 months before inclusion.
- •Patients should be in stable remission (defined as the absence of signs or symptoms of GCA and normal C-Reactive Protein (<1mg/dl), off glucocorticoids for at least 1 months at screening.
- •Willing and able to inject methotrexate or placebo subcutaneously at randomization
- •Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)
排除标准
- •Severe renal (glomerular filtration rate <30/min) failure
- •Conditions other than GCA requiring continuous or intermittent treatment with oral or parenteral Glucocorticoids unless the last exposure to Glucocorticoids was >1 months before screening
- •Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
- •Current treatment with any other conventional, biologic or targeted synthetic DMARD except tocilizumab
- •Elevation of transaminases above three times the norm
- •Simultaneous participation in another clinical trial, or participation in a clinical trial taking an investigational product, up to 30 days prior to participation in this clinical trial.
- •Pregnant or breast feeding women
- •Contraindications for therapy with Methotrexate, as indicated in the summary of product characteristics
研究组 & 干预措施
Methotrexate
The patient will be treated for 12 months weekly with methotrexate. Methotrexate will be provided at a dose of 17.5mg as a pre-filled syringe for self-injection. A dose reduction to 15 mg/week in case of intolerance, elevated liver enzymes >3x upper limit of normal or to 10 mg/week if glomerular filtration rate <50/min will be possible. If glomerular filtration rate <30/min, termination of treatment.
干预措施: Methotrexate (Drug)
Placebo
Patients receive sodium chloride as a placebo subcutaneously. It will be administered in the form of a pre-filled syringe for self-injection once a week for 12 months.
干预措施: Sodium chloride (Drug)
结局指标
主要结局
Time to relapse during the 12 months treatment period
时间窗: 12 months
次要结局
- Cumulative prednisone doses at months 6, 12 and 18(18 months)
- Self-reported fatigue : FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue Scale)(18 months)
- Number of relapses per patient during the 12 months treatment period(12 months)
- Time to first, second and third relapse after randomization(18 months)
- Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab(18 months)
- Health-related quality of life: Short Form-36(18 months)
- Patient Global Assessment of disease activity (PGA)(18 months)
- Investigator reported Evaluator Global Assessment of disease activity (EGA)(18 months)
- Prevalence of aortitis at baseline and month 12 and 18 in MRI(18 months)
- Patient Assessment of pain(18 months)
- Occurrence of symptoms and signs related to Giant cell arteritis(18 months)
- Occurrence of adverse events and serious adverse events(12 months)
- Number of vasculitic vessels and change of intima-media-values of temporal and axillary arteries(18 months)
- Proportion of subjects with increased Erythrocyte Sedimentation Rate (>20mm/h) and C-Reactive Protein levels (> 10mg/L)(18 months)
研究者
Valentin Schäfer
PD Dr. med. MuDr.
University Hospital, Bonn