Rituximab Induced Remission in Patients With Chronic Inflammatory Demyelinating Polyneuropathy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Remission at 52 weeks
研究概览
简要总结
The goal of this clinical trial is to learn if the drug called rituximab causes remission in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The aim is to investigate this in two types of patients, those who are newly diagnosed, and those who are already being treated and are dependent on the current standard therapy: immunoglobulins administered through infusion (IVIg) or through injection (SCIg). The main questions this trial aims to answer are:
- To assess the effectiveness of rituximab
- Whether it is possible and useful to prescribe patients rituximab who experience a relapse after at least six months after their last rituximab treatment.
Participants will:
- Receive the drug rituximab twice at the beginning of the trial and one additional time at six months.
- The newly diagnosed patients will also start another treatment called IVIg, which a nurse will administer every three weeks during the first three to six months.
- The patients who already being treated, will continue their regular treatment, until this is slowly reduced and stopped, during months three to six.
- Visit the clinic over the course of two years, during which they will have approximately 10 visits, for checkups and tests.
- Be asked to fill in questionnaires at each visit, and be asked to have their blood drawn four times.
详细描述
Rationale For almost 30 years, CIDP treatment consists of intravenous immunoglobulins (IVIg), corticosteroids or plasma exchange. Unfortunately, both IVIg and corticosteroids are considered treatments that suppress the disease rather than cure the disease, meaning that most patients starting on IVIg will require long-term maintenance treatment to avoid a relapse. Discovery of pathogenic antibodies in some patients with CIDP and the undisputed efficacy of anti- CD20 therapy in other demyelinating diseases such as multiple sclerosis has provided new arguments to introduce anti-CD20 therapy (such as rituximab) as a treatment modality in CIDP. In addition, rituximab (RTX) if now often used for/in treatment refractory CIDP cases and a recent review of retrospective studies has suggested efficacy in this group of patients. However, RTX efficacy data on new patients starting IVIg or patients who are on maintenance IVIg treatment is largely lacking. As RTX treatment has shown to lead to long-term remission in various auto-immune diseases, the hypothesis is that RTX can prevent ongoing need of IVIg treatment in CIDP.
Objective The primary objective of this study is to assess whether adding RTX to a limited period of IVIg induction treatment leads to long-term remission and discontinuation of IVIg, reducing the inconvenience of regular Ig infusions and related health care costs. Other objectives are to explore the feasibility of introducing rituximab as alternative maintenance treatment in patients with CIDP in patients who experience a relapse after at least 6 months after last RTX treatment (long term follow-up).
Main trial endpoints The investigators will include two groups of patients, namely untreated patients (Group 1) and immunoglobulin (Ig)-dependent patients (Group 2, see below, trial population). Primary outcome for both Group 1 and 2 is remission at 52 weeks after start of RTX. For Group 1, remission is defined as sustained improvement, without the need for further treatment. Improvement will be defined as decrease in disability by at least the minimal clinical important difference (MCID) on the adjusted INCAT (aINCAT) disability scale and/or the Inflammatory-Rasch Overall Disability Scale (IRODS).
Sustained is defined as no deterioration after maximal improvement achieved in week 13 to 26. For Group 2, remission is defined as no change in disability (MCID) between start of Ig withdrawal and week 52. Patients will be considered as a treatment failure if they do not meet the criteria for remission, or if they receive any immunomodulatory treatment for CIDP except RTX after discontinuation of induction treatment (Group 1), or withdrawal of maintenance Ig treatment (Group 2).
Other trial endpoints These will include various impairment measures, pain, fatigue, quality of life and adverse events. Endpoints will be assessed at 52 and 104 weeks, or earlier if a preliminary endpoint (relapse) is reached within the first year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Paranodopathy with demonstrated (paranodal) antibodies, previously considered part of CIDP spectrum (in these cases rituximab is preferred treatment)
- •Use of drugs associated with a demyelinating neuropathy in the last six months.
- •Known serious adverse events with previous IVIg or RTX treatment. Hypersensitivity to RTX or any component of the formulation. Hypersensitivity to the human immunoglobulins or to any of the excipients. Known selective IgA deficiency patients who developed antibodies to IgA.
- •Positive hepatitis B and C serology suggesting active/untreated infection (HBsAg, anti-HB core en anti-HBs and HCV antibody (IgG))
- •Ongoing immunosuppressive treatment for other indications.
- •Immunosuppressive treatment other than (already discontinued) corticosteroids in last 6 months.
- •IVIg interval of once every 6 weeks or more than 6 weeks (applies to Group 2 only)
- •Obesity (BMI > 35)
- •Known active malignancy (not in remission), currently treated with chemotherapy or immunomodulatory drugs, or with a life expectancy of less than 1 year.
- •History of recurrent/chronic infections
- •Active, severe infections (such as tuberculosis, sepsis and opportunistic infections)
- •Patients in a severely immunocompromised state Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- •Serious co-morbidity as judged by treating physician.
- •Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study.
- •No written informed consent
研究组 & 干预措施
Single arm: all patients receive rituximab
All patients will receive rituximab at baseline (1000 mg) and after two weeks (1000 mg). Then, depending of whether the patient shows improvement in the following three to six months, the patient will receive another dose of rituximab (500 mg) at six months.
干预措施: Rituximab (Mabthera) (Drug)
结局指标
主要结局
Remission at 52 weeks
时间窗: Baseline to 52 weeks
In order to assess efficacy of RTX: Remission at 52 weeks after start of RTX, i.e., no need of additional treatment after RTX treatment. For Group 1, remission is defined as sustained improvement, without the need for further treatment. Improvement will be defined as decrease in disability by at least the minimal clinical important difference (MCID) on the adjusted INCAT (aINCAT) disability scale and/or the Inflammatory-Rasch Overall Disability Scale (I-RODS). Sustained is defined as no deterioration after maximal improvement achieved in week 13 to 26. For Group 2, remission is defined as no change in disability (MCID) between start of Ig withdrawal and week 52.
次要结局
未报告次要终点
研究者
Filip Eftimov
Principal Investigator, MD PHD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)