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 Purpose:

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

Study Status:

Recruiting

Disease:

Amyotrophic Lateral Sclerosis

Study Type:

Interventional

Type of Intervention:

Drug

Intervention Name:

IL-2

Placebo:

No

Phase:

Phase 2

Study Chair(s)/Principal Investigator(s):

Dongsheng Fan, Peking University Third Hospital

Clinicaltrials.gov ID:

NCT04952155

Neals Affiliated?

No

Coordinating Center Contact Information

Dongsheng Fan / email hidden; JavaScript is required / +86 13701023871

Full Study Summary:

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 Sponsor:

Peking University Third Hospital

Estimated Enrollment:

13

Estimated Study Start Date:

01 / 01 / 2020

Estimated Study Completion Date:

12 / 31 / 2022

Posting Last Modified Date:

08 / 18 / 2021

Date Study Added to neals.org:

07 / 07 / 2021

Minimum Age:

18 Years

Maximum Age:

70 Years

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.

Peking University Third Hospital | Recruiting

Dongsheng Fan

Beijing, Beijing 100098
China