A Single-center, Open-label Clinical Study to Evaluate the Efficacy and Safety of Low-dose IL-2 in the Treatment of Immune-associated ALS Syndrome
试验速览
- 阶段
- 2 期
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- ALSFRS-R score
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of low-dose IL-2 in the treatment of immunorelated ALS syndrome.
详细描述
This is a single-center, open-label, self-controlled clinical study with a sample size of 10 patients for 48 weeks, including 24 weeks of administration, and 24 weeks of follow-up. During the administration period, medication was given for 2 weeks and rest for 2 weeks, as a course of treatment, with a total of 6 courses for 24 weeks. During the administration period, the drug was given on alternate days, and IL-2 1mIU was subcutaneously injected the next day for 7 times, and then rested for 2 weeks, and the cycle was repeated for 6 times. The primary outcome index was the change in the rate of ALSFRS-R score between administration period and follow-up period. Secondary outcome measures included changes in the rate of ALSAQ-40 score, ROADS score, MRC score, survival time, FVC%, Treg and CD4+ T cell subsets, inflammatory factors, serum and cerebrospinal fluid NFL during follow-up versus administration , changes in the inhibition function of Treg; Exploratory outcome indicators included the change degree of compound muscle action potential (CMAP) amplitude, quantitative analysis of corneal nerve morphologic changes by corneal confocal microscopy (CCM), Treg single-cell sequencing transcriptome analysis. The related safety indexes were also evaluated.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years old;
- •Clinically diagnosed with ALS syndrome, i.e., with ALS -like manifestations, consisting of a combination of upper and/or lower motor neuron damage;
- •significant abnormalities with rheumatoid immune-related indicators, or diagnoses of immune-mediated ALS syndrome, including but not limited to multifocal motor neuropathy (MMN), Lewis-Sumner syndrome, and other ALS-like syndromes with an immune background that cannot be clearly classified;
- •Poor treatment with conventional hormones or gamma globulin;
- •Permitted concomitant treatment: oral prednisone or equivalent doses of other glucocorticoids (≤1.0mg/kg/d); Oral routine dose of immunosuppressants or immunomodulators, such as cyclophosphamide, tacrolimus, etc.; Routine oral doses such as too much force; Doses and types of accompanying therapeutic drugs should not be changed from the trial enrollment to the end of follow-up.
- •For women of reproductive age, contraception for at least 2 weeks at the time of enrolment and negative urine HCG;
- •Reasonable and effective contraceptive measures should be taken by subjects of childbearing age from the time of trial enrollment to the end of follow-up;
- •Signed informed consent.
排除标准
- •Allergic or intolerance to IL2;
- •Receive non-standard treatment or use of excessive dose of glucocorticoids or gamma globulin intravenously within 2 months before enrollment;
- •Vaccination within 6 months before enrolment or between enrolment and the end of follow-up;
- •Peripheral venous white blood cells < 2000/mm3, lymphocytes < 600/mm3, platelets < 80,000 /mm3;
- •Complicated with severe infection or inflammation, such as bacteremia, sepsis, etc.;
- •Complicated blood system diseases, infectious diseases (hepatitis, HIV, tuberculosis, etc.), mental diseases, dementia, severe hypotension, substance abuse history, malignant tumor history, organ transplantation history, etc.;
- •Severe liver, kidney, lung or heart dysfunction: heart failure (≥NYHA grade III), renal insufficiency (creatinine clearance ≤30ml/min), abnormal liver function (3 times the upper limit of normal >);
- •Pregnant and lactating women;
- •Currently participating in other clinical studies or using other investigational drugs.
研究组 & 干预措施
IL-2
The administration period was divided into 6 courses. 6 cycles of IL-2 were administered subcutaneously at a dose of 1 million IU every other day for 2 weeks, followed by a 2-week break in treatment.
干预措施: IL-2 (Drug)
结局指标
主要结局
ALSFRS-R score
时间窗: week 0，week 24 and week 48
Changes in the rate of ALSFRS-R score during administration period compared with follow-up period
次要结局
- MRC score(week 0，week 24 and week 48)
- ALSFRS-R score(week 0，week 24 and week 48)
- ALSAQ-40 score(week 0，week 24 and week 48)
- NFL in the serum and cerebrospinal fluid(week 0，week 24 and week 48)
- ROADS score(week 0，week 24 and week 48)
- Immunological Responses(week 0 and week 24)