Low Dose IL-2 in the Treatment of Immune-associated ALS Syndrome
Study Details
Study Description
Brief Summary
The purpose of this study was to evaluate the efficacy and safety of low-dose IL-2 in the treatment of immunorelated ALS syndrome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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. The adminstration course was 24 weeks.. The 24-week follow-up period was followed after the treatment.
|
Outcome Measures
Primary Outcome Measures
- ALSFRS-R score [week 0，week 24 and week 48]
Changes in the rate of ALSFRS-R score during administration period compared with follow-up period
Secondary Outcome Measures
- ALSFRS-R score [week 0，week 24 and week 48]
Changes in the slope of ALSFRS-R score during adminstration period compared with the follow-up period
- ROADS score [week 0，week 24 and week 48]
Changes in the rate of ROADS score during adminstration period compared with the follow-up period
- ALSAQ-40 score [week 0，week 24 and week 48]
Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period
- MRC score [week 0，week 24 and week 48]
Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period
- Immunological Responses [week 0 and week 24]
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.
- NFL in the serum and cerebrospinal fluid [week 0，week 24 and week 48]
Eligibility Criteria
Criteria
Inclusion Criteria:
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18-70 years old;
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Clinically diagnosed with ALS syndrome, i.e., with ALS -like manifestations, consisting of a combination of upper and/or lower motor neuron damage;
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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;
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Poor treatment with conventional hormones or gamma globulin;
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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.
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For women of reproductive age, contraception for at least 2 weeks at the time of enrolment and negative urine HCG;
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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;
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Signed informed consent.
Exclusion Criteria:
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Allergic or intolerance to IL2;
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Receive non-standard treatment or use of excessive dose of glucocorticoids or gamma globulin intravenously within 2 months before enrollment;
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Vaccination within 6 months before enrolment or between enrolment and the end of follow-up;
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Peripheral venous white blood cells < 2000/mm3, lymphocytes < 600/mm3, platelets < 80,000 /mm3;
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Complicated with severe infection or inflammation, such as bacteremia, sepsis, etc.;
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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.;
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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 >);
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Pregnant and lactating women;
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Currently participating in other clinical studies or using other investigational drugs.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Third Hospital | Beijing | Beijing | China | 100098 |
Sponsors and Collaborators
- Peking University Third Hospital
Investigators
- Principal Investigator: Dongsheng Fan, Peking University Third Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M2020420