Efficacy and Safety of Low-Dose IL-2 in Neuromyelitis Optica Spectrum Disorder

Phase 2Not Yet RecruitingNCT07809724

Peking University People's Hospital60 enrolled

Overview

Interleukin-2 (IL-2) is an essential cytokine for T-cell proliferation. Low-dose IL-2 has been shown to increase the proportion of regulatory T cells (Tregs), negatively regulate effector T cells such as Th17 and Tfh cells, and improve the peripheral Treg/Th17 balance, thus restoring immune homeostasis. Studies have demonstrated a positive correlation between the Th17/Treg ratio and the severity of various autoimmune diseases. Clinically, low-dose IL-2 has been successfully used in the treatment of diseases such as systemic lupus erythematosus and Sjögren's syndrome. However, the efficacy and safety of IL-2 in neuromyelitis optica spectrum disorder (NMOSD) remain unknown. This clinical trial aims to investigate the safety and biological efficacy of IL-2 in treating NMOSD.

In the NMOSD-IL2 trial, 60 patients with NMOSD will participate in a randomized, double-blind, placebo-controlled clinical study. The participants will be allocated in a 1:1 ratio to the intervention and placebo groups, with 30 patients in each group. The intervention group will receive subcutaneous injections of IL-2 (1 MIU) every other day for 4 weeks, followed by twice-weekly injections for an additional 20 weeks. The placebo group will receive parallel dosing. The primary efficacy criteria will be the percentage change in Treg levels relative to baseline at week 4, indicating the biological response to IL-2. Secondary efficacy endpoints will include: (i) the maintenance of regulatory T cells during the 24 weeks treatment period with low-dose IL-2 compared to placebo, and (ii) disease activity and relapse rates, as assessed by clinical scores and MRI evaluations, in the IL-2 treatment group compared to the placebo group. Expected impact: This trial will determine whether NMOSD responds to IL-2 therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age: 18 to 74 years, inclusive at the time of informed consent. * Diagnosed with NMOSD according to the 2015 international consensus diagnostic criteria for NMOSD. * Expanded Disability Status Scale (EDSS) score between 0 and 6.5. * For women of childbearing potential, contraception must be used for more than 2 weeks after meeting the inclusion criteria, and HCG must be negative at the time of enrollment. * Able to provide written informed consent and demonstrate the ability and willingness to comply with the study protocol requirements. Exclusion Criteria: * Any prior history of receiving whole-body irradiation or bone marrow transplantation. * Any treatment with investigational drugs within 3 months prior to baseline. * Pregnancy or breastfeeding. * Any surgical procedure within 4 weeks prior to baseline (except minor surgeries). * Evidence of other demyelinating diseases or progressive multifocal leukoencephalopathy (PML). * Evidence of severe uncontrolled comorbidities that may hinder participation. * Other neurological disorders, hematological / hematopoietic disorders, congenital/acquired severe immunodeficiencies. * Heart failure (≥NYHA Class III), renal insufficiency, liver insufficiency, or respiratory failure. * White blood cell count \<3000/ml, lymphocyte count \<1000/ml, platelet count \<150,000/ml. * Evidence of chronic active hepatitis B or C. * Substance abuse or alcoholism history within 1 year prior to baseline. * Evidence of active tuberculosis (excluding participants undergoing chemoprophylaxis for latent tuberculosis infection). * Intolerance to IL-2: hypersensitivity reactions to the active substance or any of its excipients (e.g. shock, allergic reactions). * Active suicidal ideation within the past 6 months before screening, or a history of suicide attempts within the past 3 years.

Outcomes

Primary Outcomes

Change in the percentage of Tregs at week 4 compared to baseline (week 0)

expressed as a percentage of the total CD4+ cells

Time frame: Week 4

Secondary Outcomes

Change in the percentage of Tregs at week 2 compared to baseline (week 0)

expressed as a percentage of the total CD4+ cells

Time frame: Week 2

Change in the percentage of Tregs at week 24 compared to baseline (week 0)

expressed as a percentage of the total CD4+ cells

Time frame: Week 8, 12, 16, 20, 24

Change of Th1, Th2, and Th17 cells to low-dose IL-2 compared to baseline (week 0)

expressed as a percentage of the total CD4+ cells

Time frame: Week 2, 4, 8, 12, 16, 20, 24

Cumulative number of active MRI lesions and/or changes in orbital optic nerve MRI lesions

Measure the number of new gadolinium-enhancing lesions and new or enlarged T2 lesions using MRI.

Time frame: Week 24

Change of cumulative total activity (CUA)

Cumulative number of new Gd-enhanced T1-weighted lesions and new or enlarged T2-weighted lesions, without repeat counting

Time frame: Week 24

Change in the Expanded Disability Status Scale (EDSS) compared to baseline (week 0)

The Expanded Disability Status Scale (EDSS) ranges from 0 to 10, with higher scores indicating greater neurological disability and a worse outcome. A score of 0 indicates a normal neurological examination, whereas a score of 10 indicates death due to neurological disease. Change from baseline will be calculated as the score at each follow-up visit minus the baseline score; a negative change indicates improvement and a positive change indicates worsening.

Time frame: Week 4, 8, 16, 24

Change in the Modified Rankin Scale (mRS) score compared to baseline (week 0)

The Modified Rankin Scale (mRS) ranges from 0 to 6, with higher scores indicating greater disability and a worse outcome. A score of 0 indicates no symptoms, whereas a score of 6 indicates death. Change from baseline will be calculated as the score at each follow-up visit minus the baseline score; a negative change indicates improvement and a positive change indicates worsening.

Time frame: Week 4, 8, 16, 24

Percentage of patients with relapses

Time frame: Week 24

Percentage of disease free patients, defined as those with no clinical symptoms and no active lesions on MRI

Time frame: Week 24

Safety endpoints: IL-2-related adverse events

Assessment of IL-2-related adverse events (AEs) and recording of the AE incidence.

Time frame: Week 2, 4, 8, 12, 24

Efficacy and Safety of Low-Dose IL-2 in Neuromyelitis Optica Spectrum Disorder

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts