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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

IL-2

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Peking University Third HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IL-2

Arm Description

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.

Outcomes

Primary Outcome Measures

ALSFRS-R score

Changes in the rate of ALSFRS-R score during administration period compared with follow-up period

Secondary Outcome Measures

ALSFRS-R score

Changes in the slope of ALSFRS-R score during adminstration period compared with the follow-up period

ROADS score

Changes in the rate of ROADS score during adminstration period compared with the follow-up period

ALSAQ-40 score

Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period

MRC score

Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period

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.

NFL in the serum and cerebrospinal fluid

Full Information

NCT ID

NCT04952155

First Posted

June 27, 2021

Last Updated

August 11, 2021

Sponsor

Peking University Third Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04952155

Brief Title

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

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2020 (Actual)

Primary Completion Date

December 31, 2021 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Peking University Third Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

IL-2

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

IL-2

Intervention Description

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.

Primary Outcome Measure Information:

Title

ALSFRS-R score

Description

Changes in the rate of ALSFRS-R score during administration period compared with follow-up period

Time Frame

week 0，week 24 and week 48

Secondary Outcome Measure Information:

Title

ALSFRS-R score

Description

Changes in the slope of ALSFRS-R score during adminstration period compared with the follow-up period

Time Frame

week 0，week 24 and week 48

Title

ROADS score

Description

Changes in the rate of ROADS score during adminstration period compared with the follow-up period

Time Frame

week 0，week 24 and week 48

Title

ALSAQ-40 score

Description

Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period

Time Frame

week 0，week 24 and week 48

Title

MRC score

Description

Changes in the rate of ALSAQ-40 score during adminstration period compared with the follow-up period

Time Frame

week 0，week 24 and week 48

Title

Immunological Responses

Description

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.

Time Frame

week 0 and week 24

Title

NFL in the serum and cerebrospinal fluid

Time Frame

week 0，week 24 and week 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dongsheng Fan

Phone

+86 13701023871

dsfan@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dongsheng Fan

Organizational Affiliation

Peking University Third Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking University Third Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100098

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dongsheng Fan

12. IPD Sharing Statement

Plan to Share IPD

Yes

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

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