Clinical trial NCT04952155: Low Dose IL-2 in the Treatment of Immune-associated ALS Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2021-07-07
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ALSFRS-R score
timeFrame: week 0，week 24 and week 48
Secondary outcomes:
measure: ALSFRS-R score
timeFrame: week 0，week 24 and week 48
measure: ROADS score
timeFrame: week 0，week 24 and week 48
measure: ALSAQ-40 score
timeFrame: week 0，week 24 and week 48
measure: MRC score
timeFrame: week 0，week 24 and week 48
measure: Immunological Responses
timeFrame: week 0 and week 24
measure: NFL in the serum and cerebrospinal fluid
timeFrame: week 0，week 24 and week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
Study officials:
affiliation: Peking University Third Hospital
name: Dongsheng Fan
role: PRINCIPAL_INVESTIGATOR
References: