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

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04952155
• Other study ID #: M2020420
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2021
• Source: Peking University Third Hospital
• Contact: Dongsheng Fan
• Phone: +86 13701023871
• Email: dsfan[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 13
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

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.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Third Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	NFL in the serum and cerebrospinal fluid		week 0,week 24 and week 48