Low Dose IL-2 in the Treatment of Immune-associated ALS Syndrome

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of low-dose IL-2 in the treatment of immunorelated ALS syndrome.

Detailed Description
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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.

Official Title
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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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL-2<br>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. | Drug: IL-2<br>* 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. The adminstration course was 24 weeks.. The 24-week follow-up period was followed after the treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALSFRS-R score | Changes in the rate of ALSFRS-R score during administration period compared with follow-up period | week 0，week 24 and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALSFRS-R score | Changes in the slope of ALSFRS-R score during adminstration period compared with the follow-up period | week 0，week 24 and week 48 | 
| ROADS score | Changes in the rate of ROADS score during adminstration period compared with the follow-up period | week 0，week 24 and week 48 | 
| ALSAQ-40 score | Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period | week 0，week 24 and week 48 | 
| MRC score | Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period | week 0，week 24 and week 48 | 
| Immunological Responses | Analysis regulatory CD4+ T (Treg) cells , interleukin 17 (IL-17)-producing helper T (Th17) cells，Teff cells，follicular helper T (Tfh) cells and related cytokines before and during IL-2 treatment. | week 0 and week 24 | 
| NFL in the serum and cerebrospinal fluid |  | week 0，week 24 and week 48 |