NCT03864185已完成2 期
The Evaluation of Efficacy and Safety of Rituximab (Genetical Recombination) in Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Patients With Immunoglobulin G4 (IgG4) Autoantibodies in the Exploratory Clinical Trial
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale
研究概览
简要总结
To evaluate the efficacy and safety of rituximab (genetical recombination) intravenously administered to CIDP patients with positive or negative IgG4 autoantibody.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with definite CIDP diagnosed according to the modified diagnostic criteria of European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) (2010) by the time of enrollment in the study
- •Patients meeting one of the following conditions:
- •(i) Patients with positive serum IgG4 autoantibody (CNTN-1 or NF-155) confirmed by the time of enrollment in the study
- •(ii) Patients with negative serum IgG4 autoantibody (CNTN-1 and NF-155) confirmed by the time of enrollment in the study
- •Patients with refractory CIDP not responding adequately to treatment with corticosteroid for 12 weeks, and intravenous immunoglobulin therapy (IVIg) for 8 weeks by the time of enrollment in the study, or those who are unable to administer or continue corticosteroid and IVIg
- •Patients with total adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale scores of 2 to 8 at both preliminary enrollment and enrollment, and with the total score at enrollment equal to or worse than that at preliminary enrollment
- •Patients aged 12 years or older at informed consent
- •Patients who give their voluntary written consent after having received adequate information on this study (legally acceptable representatives should also give consent for underage patients, and informed assent should be obtained from children aged 12 to 15)
排除标准
- •Patients with disease meeting one of the following exclusion criteria defined in the modified EFNS/PNS diagnostic criteria (2010).
- •(i) Borrelia burgdorferi infection (Lyme disease), diphtheria, drug or toxin exposure probably to have caused the neuropathy Hereditary demyelinating neuropathy
- •(ii) Prominent sphincter disturbance
- •(iii) Diagnosis of multifocal motor neuropathy
- •(iv) IgM monoclonal gammopathy with high titre antibodies to myelin-associated glycoprotein
- •(v) Other causes for a demyelinating neuropathy including POEMS syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy PNS lymphoma and amyloidosis may occasionally have demyelinating features
- •Patients who have started or have increased the dose of corticosteroid for CIDP within 12 weeks prior to the enrollment
- •Patients who have started or have increased the dose of IVIg within 8 weeks prior to the enrollment
- •Patients who have underwent plasmapheresis within 8 weeks prior to the enrollment or patients with refractory disease not responding adequately to 8 weeks of plasmapheresis (plasma exchange or double-filtration plasmapheresis)
- •Patients who have started or have increased the dose of an immunosuppressant (azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, interferon alpha, interferon beta, etanercept, methotrexate, mitoxantrone, alemtuzumab, cladribine, tacrolimus, fingolimod) within 12 weeks prior to the enrollment
- •Patients who have underwent hematopoietic stem cell transplant prior to the enrollment
- •Patients who have used rituximab (genetical recombination) prior to the enrollment
- •Patients who have participated in another clinical study within 3 months prior to the enrollment (enrollment is allowed for those participating in a clinical study in the range of Indications or Dosage and Administration in Japan) or patients who are participating in another study
- •Patients with poorly controlled diabetes (HbA1c of 7 % or higher)
- •Patients who have or are suspected to have active infection (infection requiring treatment with systemic antimicrobial, antifungal, or antiviral agents) at the time of the enrollment
- •Patients tested positive for HBs antigen, HBs antibody, HBc antibody, and/or HCV antibody (patients with positive HBs antibody or HBc antibody can be enrolled when a hepatitis B virus-DNA test is negative [below the limit of detection], and hepatitis B virus-DNA and aspartate/alanine transaminase levels are monitored at fixed intervals), or patients with positive HIV antibody or HTLV-1 antibody at the time of the enrollment
- •Patients with leukopenia (less than 2,000 /mm3), neutropenia (less than 1,000 /mm3), or lymphopenia (less than 500 /mm3) at the time of the enrollment
- •Patients with history of serious hypersensitivity or anaphylactic reaction to one of the ingredients in the investigational drug or murine protein-containing products
- •Patients with serious comorbidity (e.g., hepatic, renal, cardiac, lung, hematologic, or brain disease)
- •Female patients who are pregnant, lactating, or potentially pregnant, or patients who are not willing to use contraceptive measures during the study period
- •Patients who are judged to be unsuitable by the investigator or a sub-investigator
结局指标
主要结局
Rate of patients with improvement in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale
时间窗: Up to 52 weeks
Primary analysis will compare scores of adjusted INCAT Disability Scale evaluated prior to treatment (at the time of enrollment) and scores at each timepoint after week 26 to calculate the proportion of patients who achieve an improvement of one and more from the baseline. The INCAT Disability Scale is an index to evaluate disorders in lower (gait) and upper (elevation of the upper arms and fine movement of the fingertips) extremities. The INCAT score is a 10-point scale and ranges from 0 (normal) to 10 (worst). For the "adjusted" INCAT score, a change in upper extremity score from 0 to 1 or 1 to 0 will not be considered meaningful in this evaluation.
次要结局
- Change in Rasch-built Overall Disability Scale (R-ODS) score(Up to 52 weeks)
- Change in Medical Research Council (MRC) Sum Score(Up to 52 weeks)
- Change in motor nerve distal latency(Up to 52 weeks)
- Change in motor nerve proximal latency(Up to 52 weeks)
- Cerebrospinal fluid protein level(Up to 52 weeks)
- B cell counts (CD19 positive and CD20 positive cell counts) and T cell counts (CD3 positive, CD4 positive, and CD8 positive cell counts)(Up to 52 weeks)
- Serum antibody titers of IgG4 (CNTN-1 and NF-155) and these IgG subclass(Up to 52 weeks)
- Expression of HACA(Up to 52 weeks)
- Maximum serum concentration (Cmax) of rituximab (genetical recombination)(Up to 52 weeks)
- Half-life (t1/2) of rituximab (genetical recombination)(Up to 52 weeks)
- Clearance (CL) of rituximab (genetical recombination)(Up to 52 weeks)
- Mean residence time (MRT) of rituximab (genetical recombination)(Up to 52 weeks)
- Volume of distribution (Vds) of rituximab (genetical recombination) level(Up to 52 weeks)
- Serum neurofilament(Up to 52 weeks)
- Change in grip strength (kPa)(Up to 52 weeks)
- Change in motor nerve compound muscle action potential (CMAP)(Up to 52 weeks)
- Change in motor nerve conduction velocity(Up to 52 weeks)
- Serum rituximab (genetical recombination) level(Up to 52 weeks)
- Area under the curve (AUC) of blood concentration of rituximab (genetical recombination)(Up to 52 weeks)
研究者
Masahiro Iijima
Designated Associate Professor
Nagoya University
研究点 (5)
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