Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder

Summary

Study Title: A National, Multicenter, Randomized Controlled Trial of the Modified Zipper Therapy in AQP4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (ELITE Study)

Brief Summary:

The goal of this clinical trial is to evaluate the efficacy and safety of a novel sequential immunomodulation strategy, termed "Modified Zipper Therapy," in patients with acute attacks of Aquaporin-4 antibody-positive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD). The therapy aims to enhance neurological recovery by combining plasma exchange (PE) with immediate complement inhibition using eculizumab, following high-dose corticosteroid pulse therapy.

The main questions this trial aims to answer are:

Efficacy: Does the Modified Zipper Therapy (high-dose corticosteroids + plasma exchange + eculizumab) lead to a higher rate of neurological improvement at Week 12 compared to standard therapy (high-dose corticosteroids + plasma exchange alone)?

For patients with NMOSD-related optic neuritis (NMOSD-ON), improvement is defined as a gain of ≥10 letters on the ETDRS chart or a decrease of ≥0.2 LogMAR in best-corrected visual acuity (BCVA).

For patients with NMOSD-related longitudinally extensive transverse myelitis (NMOSD-LETM), improvement is defined as a reduction of ≥2 points on the Expanded Disability Status Scale (EDSS).

Safety: What is the nature and frequency of adverse events experienced by participants receiving the Modified Zipper Therapy compared to those receiving standard therapy?

Researchers will compare the Modified Zipper Therapy group to the Standard Therapy group to see if the novel combination is more effective in improving visual and functional outcomes in acute AQP4-IgG+ NMOSD.

Participants will:

Be randomly assigned (like a coin toss) to receive either the Modified Zipper Therapy or the Standard Therapy.

Undergo a treatment period involving intravenous corticosteroids and a series of plasma exchange sessions. The Modified Zipper Therapy group will also receive intravenous eculizumab infusions timed around the plasma exchange procedures.

Be followed for 24 weeks after treatment completion.

Attend scheduled clinic visits for comprehensive assessments including:

Visual acuity testing (using ETDRS, Snellen, and low-contrast charts).

Neurological function evaluations (EDSS and OSIS scores).

Optical coherence tomography (OCT) and visual evoked potential (VEP) tests.

Magnetic resonance imaging (MRI) scans of the optic nerves.

Safety monitoring (physical exams, lab tests, ECGs).

Conditions

• Neuromyelitis Optica Spectrum Disorders (NMOSD)

Interventions

BIOLOGICAL

Eculizumab administration

Complement Inhibitor Therapy (Eculizumab): Initial Dose: Administer 900 mg of eculizumab intravenously immediately after the first PE session. Supplemental Doses: Administer supplemental doses (300-600 mg) after the 2nd, 3rd, and 4th PE sessions. The exact dose will be adjusted in real-time based on drug clearance post-PE. Maintenance Therapy: Administer three additional 900 mg intravenous infusions on the day of the last PE session, and at the 1st and 2nd weeks after its completion, to consolidate efficacy and maintain stable complement inhibition.

DRUG

High-dose corticosteroid pulse therapy

High-Dose Corticosteroid Pulse: Intravenous methylprednisolone (IVMP) 1000 mg daily for 3 days, then 500 mg daily for 3 days, followed by 250 mg daily for 3 days, and finally 125 mg daily for 3 days. Subsequently, switch to oral prednisone at 1 mg/kg/day, tapered by 5 mg weekly until a maintenance dose of 10 mg/day is reached, which is continued for 6 months.

PROCEDURE

Plasma exchange (PE)

Plasma Exchange (PE) Therapy: Initiated concurrently with corticosteroids. Perform at least 5 PE sessions every other day. Each session exchanges 1.0-1.5 times the plasma volume. Treatment intervals may be adjusted based on fibrinogen levels and bleeding risk.

Sponsors & Collaborators

• Tianjin Medical University General Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2026-12-31

Completion

2027-06-30

Countries

• China

Study Locations