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

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

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 Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: IL-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 Type: Interventional
• Enrollment (Anticipated): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100098
      • Recruiting
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: June 27, 2021
• First Posted (ACTUAL): July 7, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: M2020420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No