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

Efficacy and Safety of Low-Dose IL-2 in Neuromyelitis Optica Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Phase II Trial

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.

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.