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

Official title

Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Randomized Controlled Trial Study

Overview

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).

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 conso
• 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.

Primary outcome measures

• Best corrected visual acuity [Time frame: Baseline, Week 12]
• Expanded Disability Status Scale (EDSS) [Time frame: Baseline, Week 12]

Secondary outcome measures (10)

• Best corrected visual acuity [Time frame: Baseline, Week 4, Week 24,]
• Expanded Disability Status Scale (EDSS) [Time frame: Baseline, Week 4, Week 24,]
• Optic-Spinal Impairment Score(OSIS) [Time frame: Baseline, Week 4, Week 12, Week 24]
• Visual Evoked Potential P100 Wave Latency [Time frame: Baseline, Week 12, Week 24]
• Visual Evoked Potential P100 Wave Amplitude [Time frame: Baseline, Week 12, Week 24]
• Retinal nerve fiber layer (RNFL) thickness [Time frame: Baseline, Week 12, Week 24,]
• Ganglion Cell-Inner Plexiform Layer (GCIPL) Thickness [Time frame: Baseline, Week 12, Week 24]
• Cross-sectional area of the optic nerve [Time frame: Baseline, Week 12, Week 24]
• Length of Optic Nerve Lesion [Time frame: Baseline, Week 12, Week 24]
• Concentration of serum sC5b-9 [Time frame: Baseline, Week 4, Week 12, Week 24]

Eligibility criteria

Inclusion criteria

• Participants ≥ 18 years of age
• Definite diagnosis according to the 2015 IPND diagnostic criteria for AQP4-IgG-positive NMOSD
• Seropositivity for anti-AQP4 antibody.
• Time from onset to enrollment ≤ 30 days.
• For patients with optic neuritis: visual acuity ≤ 20/200 at screening; for relapse cases, baseline visual acuity prior to this acute episode must have been ≥ 20/60.
• For patients with longitudinal extensive transverse myelitis (LETM): EDSS score ≥ 5.5 at screening; for relapse cases, baseline EDSS score prior to this acute episode must have been ≤ 3.5.
• Ability to understand and voluntarily provide written informed consent-

Exclusion criteria

• Patients with concurrent neuromuscular disorders.
• Patients with severe coagulation dysfunction.
• Patients with known allergy to plasma or intravenous immunoglobulin (IVIG).
• Patients with active hepatitis B or C virus infection, human immunodeficiency virus (HIV) infection, or those deemed at high risk for the onset or reactivation of syphilis or tuberculosis at screening.
• Patients with active systemic infection at screening, or a history of severe chronic or recurrent infections.
• Pregnant or lactating patients.
• Patients with chronic, severe medical conditions that may affect study compliance.
• Patients with any clinically significant abnormal laboratory findings as determined by the investigator (e.g., severe anemia, leukopenia, thrombocytopenia, etc.).
• Patients whom the investigator considers unlikely to complete the study or unlikely to comply with the study requirements (for administrative reasons or otherwise).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University General Hospital, Department of Neurology — Tianjin

Identifiers

NCT: NCT07420296 · IRB2025-YX-575-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗