Acute treatments for AQP4-positive NMOSD attacks

Eculizumab Add-On Therapy in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Multicenter Prospective Real-World Study

This project will test whether adding eculizumab or IVIG to high-dose IV steroid pulses helps adults with AQP4-positive NMOSD during an acute attack.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: eculizumab
• Locations: 1 site (Beijing)
• Trial ID: NCT07410039 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective, real-world cohort of Chinese adults with AQP4-IgG–positive NMOSD presenting within 21 days of an optic neuritis or transverse myelitis attack. Based on patient preference, participants receive one of three acute-phase regimens: eculizumab plus IV methylprednisolone, IVIG plus IV methylprednisolone, or IV methylprednisolone alone. Clinical outcomes and safety data are collected and compared across the groups in a Phase 4 post-marketing context. The observational, non-randomized design reflects routine care rather than a blinded intervention.

Who should consider this trial

Good fit: Adults aged 18–65 with IPND-defined NMOSD who are AQP4-IgG positive and within 21 days of a new or worsening optic neuritis or transverse myelitis attack are the intended participants.

Not a fit: Patients who are AQP4-IgG negative, outside the 21-day acute window, under 18 or over 65, or with contraindications to eculizumab, IVIG, or high-dose steroids are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding eculizumab or IVIG to standard IV steroid pulses could improve recovery from acute NMOSD attacks and reduce short-term disability.

How similar studies have performed: Complement inhibitors such as eculizumab have shown clear benefit for relapse prevention in AQP4-positive NMOSD, but their use as an add-on during the acute attack phase is less well established while IVMP and IVIG are established acute therapies.

Eligibility criteria

Inclusion Criteria:

1. Age: 18 - 65 years old, gender not restricted.
2. Patients who meet the diagnostic criteria for NMOSD as set by the International Panel for NMO Diagnosis (IPND) in 2015, and have positive serum AQP4-IgG (by CBA method or live cell method).
3. Acute phase of NMOSD-ON, defined as new or worsening optic nerve dysfunction (visual acuity decline accompanied or not by eye pain and visual field defect), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent optic nerve damage on imaging (new or expanded T2WI lesions, with enhancement); the best corrected visual acuity (BCVA) of the affected eye during the acute phase of NMOSD-ON (if both eyes are affected simultaneously, the worse eye is considered) drops from above 0.3 to ≤ 0.1.
4. Acute phase of NMOSD-TM, defined as new or worsening spinal cord dysfunction (limb weakness or numbness, accompanied or not by urinary and defecation disorders), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent spinal cord damage on imaging (new or expanded T2WI lesions, with enhancement); the EDSS score during the acute phase of NMOSD-TM increases from ≤ 4.0 to ≥ 6.0.
5. Clinical onset and recurrence determination requires unanimous judgment by each center and the center committee (an independent group of 3 people).
6. Agree to receive meningococcal vaccine or use eculizumab during and 2 weeks after the medication.
7. Sign the informed consent.

Exclusion Criteria:

1. Damage to the optic nerve or spinal cord caused by other non-NMOSD-related factors.
2. Abnormal laboratory indicators that need to be excluded from the subjects include, but are not limited to the following indicators:

   Neutrophils \< 1.5 × 109/L, Hemoglobin \< 90g/L, Platelet count \< 75 × 109/L; Serum creatinine \> 1.5 × ULN, Total bilirubin \> 1.5 × ULN, Aspartate aminotransferase (AST) \> 1.5 × ULN, Alanine aminotransferase (ALT) \> 1.5 × ULN, Alkaline phosphatase \> 2 × ULN ； HbA1c \> 8% (for diabetic patients); GFR \< 60 mL/minute/1.73m2.
3. Pregnant or lactating women, as well as those planning to become pregnant during the study period.
4. Those who have received PE/IA/IVIG/FcRn/B-cell deletion/C5/IL-6 treatment within 1 month before enrollment.
5. Active infections: active hepatitis B, hepatitis C, syphilis or HIV infection; active systemic infections or immunodeficiency diseases; unrelieved meningococcal infection of the meninges, or patients with severe infections that cannot use immunosuppressive drugs.
6. Patients with severe internal or external diseases (not limited to such as heart failure, unstable angina pectoris, respiratory failure, pulmonary insufficiency, cachexia, organ transplantation, etc.).
7. Those who have had or currently have an untreated malignant tumor that is not well controlled.
8. Patients with serious physical or mental diseases that may affect the smooth implementation of the study.
9. Patients known to be allergic to monoclonal drugs, murine proteins or any excipients.
10. Patients who are intolerant to methylprednisolone or gamma globulin.
11. Patients who cannot complete the magnetic resonance enhanced scan screening.
12. Patients who are participating in other interventional clinical trials.
13. Patients who cannot understand the questionnaire questions or cooperate with the questionnaire survey.
14. Situations that the research team collectively deems unsuitable for participation in this study.

Where this trial is running

Beijing

• the First Medical Center of Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Dehui huang, Doctoral degree

Conditions Neuromyelitis Optica Spectrum Disorder Attack; Neuromyelitis Optica Spectrum Disorder; acute attack phase; eculizumab add-on therapy; AQP4-IgG positive