NCT02990286已完成3 期
Evaluation of Efficacy and Safety of Rituximab in Association With Mycophenolate Mofetil Versus Mycophenolate Mofetil Alone in Patients With Interstitial Lung Diseases (ILD) Non-responders to a First-line Immunosuppressive Treatment
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 5
- 主要终点
- Change in FVC in % of predicted
研究概览
简要总结
The purpose of the study is to evaluate the efficacy on lung function 6 months after one course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one course of placebo and 6 months of MMF treatment in a broad range of patients with Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.
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
- •Age ≥ 18 years
- •A diagnosis of ILD:
- •ILD associated with differentiated CTD or IPAF (based on internationally accepted criteria)
- •OR idiopathic ILD
- •A diagnosis of NSIP based on:
- •a histological pattern of NSIP
- •OR HRCT findings suggestive of NSIP defined as basal predominant reticular abnormalities with traction bronchiectasis, peri-bronchovascular extension and subpleural sparing, frequently associated with ground-glass attenuation
- •Patients who did not respond or relapsed or were not able to continue at least one first-line immunosuppressive treatment of ILD: corticosteroids, azathioprine, cyclophosphamide or other immunosuppressants. For the assessment of clinical response, the absence of response was defined as: either a decrease or an increase, but <10% in % predicted FVC.
- •Subjects covered by or having the rights to French social security (including CMU),
- •Written informed consent obtained from subject, with a specific check box on the Consent form of the study, understanding the risk for men and women treated with mycophenolate mofetil. And additional written consent from subject on the care and contraception agreement form for women of childbearing potential treated with mycophenolate.
- •Ability for subject to comply with the requirements of the study
排除标准
- •Known diagnosis of significant respiratory disorders (asthma, tuberculosis, sarcoidosis, aspergillosis, or cystic fibrosis) other than CTD-NSIP, IPAF-NSIP and iNSIP
- •Evidence of any clinically significant, severe or unstable, acute or chronically progressive cardiac (severe heart failure New York Heart Association Class IV or severe uncontrolled cardiac disease), other medical disease (other than NSIP) or surgical disorder, or any condition that may affect patient safety in the judgment of the investigator.
- •HRCT pattern of typical usual interstitial pneumonia (UIP)
- •For patients with idiopathic ILD, HRCT pattern of possible UIP (no evocative of NSIP)
- •Histological pattern other than pattern of NSIP
- •A first line treatment with MMF or rituximab
- •Known hypersensitivity to MMF or rituximab or sulfonamide antibiotics
- •Treatment with immunosuppressive treatments other than corticosteroids:
- •azathioprine, cyclophosphamide, methotrexate, cyclosporine, tacrolimus, leflunomide within 2 weeks (5 half-lives <= 2 weeks) prior to inclusion
- •intravenous immunoglobulins, hydroxychloroquine or other monoclonal antibody therapies (such as but not limited to etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab) within 6 months (5 half-lives <= 6 months) prior to inclusion
- •Patients registered on a pulmonary transplantation list
- •Patients with known hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) hereditary deficiency (such as Lesch-Nyhan and Kelley-Seegmiller syndrome)
- •Pregnant or breastfeeding women, or women of child-bearing potential not using two reliable contraceptive methods (including female partners of sexually active men treated with mycophenolate) and men not using a contraceptive method (condom), or women and men having a pregnancy project during the year following randomization.
- •Patients at significant risk for infectious complications: HIV positive, other known immunodeficiency syndromes, untreated tuberculosis, hepatitis B and C or other known viral infection, infection requiring anti-infectious treatment in the preceding 4 weeks
- •Current history of substance and/or alcohol abuse
- •Deprivation of liberty, under judicial protection
- •Participation in another biomedical research with experimental drug or medical device
研究组 & 干预措施
Rituximab with Mycophenolate Mofetil
Experimental
干预措施: Rituximab (Drug)
Rituximab with Mycophenolate Mofetil
Experimental
干预措施: Mycophenolate Mofetil (Drug)
Placebo of rituximab with Mycophenolate Mofetil
Placebo Comparator
干预措施: Placebo of Rituximab (Drug)
Placebo of rituximab with Mycophenolate Mofetil
Placebo Comparator
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
Change in FVC in % of predicted
时间窗: From baseline to 6 months
Change in FVC (in % of predicted) since declines in FVC correlates with increased risk of subsequent mortality in ILD patients and FVC is one of the core set of outcomes defined in interstitial lung diseases. Data obtained from the two groups of patients (rituximab and placebo) will be compared to each other. FVC will be performed in each study center in a standardized manner according to the ATS/ERS recommendations and ECCS reference equations
次要结局
- Changes in gammaglobulins(Changes from baseline to 6 months in gammaglobulins)
- Changes in HRCT of the chest images(Changes from baseline to 6 months in HRCT of the chest images)
- Adverse events related to treatment(Adverse events during the 6 months of study period)
- Rituximab PK parameters : distribution volume(Points at Day1, Day15, 3 and 6 months)
- Rituximab clearance(Points at Day1, Day15, 3 and 6 months)
- Half-life of rituximab in blood(Points at Day1, Day15, 3 and 6 months)
- Progression Free Survival (PFS).(PFS measured at 3, 6 and 12 months)
- Cough evaluation(Changes from baseline to 6 months in cough evaluation)
- Changes in the quality of life score(Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough)
- Changes in the FVC expressed as % of predicted(Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted)
- Changes in the visual analogic scales of dyspnea(Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough)
- Cumulative doses of corticoids for the 2 groups(Cumulative doses of corticoids at 6 months)
- Changes in DLCO(Changes from baseline to 6 months in DLCO)
- Changes in the 6-minutes-walk test(Changes from baseline to 6 months in the 6-minutes-walk test)
- Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes(Changes from baseline to 6 months in lymphocytes B CD19)
- Changes in autoantibodies concentration(Changes from baseline to 6 months in autoantibodies concentration)
研究者
研究点 (5)
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