Modified Zipper Therapy for AQP4‑antibody–positive NMOSD acute attacks

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

This trial will test whether adding immediate eculizumab to high‑dose steroids and plasma exchange helps adults with AQP4‑antibody–positive NMOSD recover better from acute attacks.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 198 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Tianjin Medical University General Hospital (Academic / other)
• Drugs / interventions: eculizumab
• Locations: 1 site (Tianjin)
• Trial ID: NCT07420296 on ClinicalTrials.gov

What this trial studies

This is a randomized, multicenter, Phase 4 trial comparing a sequential immunomodulation approach — high‑dose corticosteroid pulse therapy followed by plasma exchange and immediate eculizumab — versus the standard sequence of corticosteroids and plasma exchange alone. Adults with confirmed AQP4‑IgG–positive NMOSD presenting within 30 days of an acute attack are enrolled and randomized to the two arms. The primary outcome is neurological improvement at Week 12, with safety monitoring focused on infectious and hematologic risks related to complement inhibition and plasma exchange. The protocol includes predefined entry criteria for severe optic neuritis and longitudinal extensive transverse myelitis and excludes patients with active chronic viral infections or severe coagulation disorders.

Who should consider this trial

Good fit: Adults (≥18 years) with AQP4‑IgG–positive NMOSD presenting within 30 days of an acute attack who meet the 2015 IPND criteria and the trial's vision or spinal cord severity thresholds are ideal candidates.

Not a fit: Patients with concurrent neuromuscular disorders, severe coagulation dysfunction, active hepatitis B or C, HIV infection, or known allergy to plasma/IVIG are excluded and are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could improve early neurological recovery after acute NMOSD attacks and reduce longer‑term disability from relapses.

How similar studies have performed: Eculizumab is proven effective for relapse prevention in AQP4‑positive NMOSD, but using immediate complement inhibition after plasma exchange to improve acute recovery is a novel strategy with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Participants ≥ 18 years of age
2. Definite diagnosis according to the 2015 IPND diagnostic criteria for AQP4-IgG-positive NMOSD
3. Seropositivity for anti-AQP4 antibody.
4. Time from onset to enrollment ≤ 30 days.
5. 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.
6. 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.
7. Ability to understand and voluntarily provide written informed consent-

Exclusion Criteria:

1. Patients with concurrent neuromuscular disorders.
2. Patients with severe coagulation dysfunction.
3. Patients with known allergy to plasma or intravenous immunoglobulin (IVIG).
4. 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.
5. Patients with active systemic infection at screening, or a history of severe chronic or recurrent infections.
6. Pregnant or lactating patients.
7. Patients with chronic, severe medical conditions that may affect study compliance.
8. Patients with any clinically significant abnormal laboratory findings as determined by the investigator (e.g., severe anemia, leukopenia, thrombocytopenia, etc.).
9. Patients whom the investigator considers unlikely to complete the study or unlikely to comply with the study requirements (for administrative reasons or otherwise).

Where this trial is running

Tianjin

• Tianjin Medical University General Hospital, Department of Neurology — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Chao Zhang

Conditions Neuromyelitis Optica Spectrum Disorders; NMOSD; Eculizumab; Plasma exchange; Corticosteroid pulse therapy; Optic neuritis; Longitudinally extensive transverse myelitis