Neuromyelitis Optica Spectrum Disorders (NMOSD)Phase 3ELITENCT07420296
Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder
A Phase 3 study testing Eculizumab administration, High-dose corticosteroid pulse therapy and Plasma exchange (PE) in people with Neuromyelitis Optica Spectrum Disorders (NMOSD), run by Tianjin Medical University General Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuromyelitis Optica Spectrum Disorders (NMOSD)
- What is being tested?
- Eculizumab administration, High-dose corticosteroid pulse therapy and Plasma exchange (PE)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2026to 30 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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-
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tianjin Medical University General Hospital, Department of Neurology
Tianjin
Chao Zhang, +8602260814587, chaozhang@tmu.edu.cn
About this study
Official title: Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Randomized Controlled Trial Study
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:
Read more
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).
- Being tested
- Eculizumab administration, High-dose corticosteroid pulse therapy, Plasma exchange (PE)
- Keywords
- NMOSD, Eculizumab, Plasma exchange, Corticosteroid pulse therapy, Optic neuritis, Longitudinally extensive transverse myelitis
- Medical subject headings
- Neuromyelitis Optica, Optic Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eculizumab administrationBiological
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.
High-dose corticosteroid pulse therapyDrug
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.
Plasma exchange (PE)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Not described Receives: Biological: Eculizumab administration; Drug: High-dose corticosteroid pulse therapy; Procedure: Plasma exchange (PE) |
| Control group | Active comparator | High-dose corticosteroid pulse therapy+ plasma exchange Receives: Drug: High-dose corticosteroid pulse therapy; Procedure: Plasma exchange (PE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best corrected visual acuity
Measured: Baseline, Week 12
Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is an ordinal scale ranging from 0 to 10, with higher scores indicating worse neurological impairment and disability in patients with neuromyelitis optica spectrum disorder (NMOSD)
Measured: Baseline, Week 12
Secondary outcomes (10)
Best corrected visual acuity
Measured: Baseline, Week 4, Week 24,
Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is an ordinal scale ranging from 0 to 10, with higher scores indicating worse neurological impairment and disability in patients with neuromyelitis optica spectrum disorder (NMOSD)
Measured: Baseline, Week 4, Week 24,
Optic-Spinal Impairment Score(OSIS)
The Optic-Spinal Impairment Score (OSIS) is a composite scale specifically designed for neuromyelitis optica spectrum disorder (NMOSD), assessing visual function (0-8), motor function (0-7), sensory function (0-5), and sphincter function (0-5). Higher scores reflect greater severity of optic and spinal cord dysfunction, indicating a worse outcome.
Measured: Baseline, Week 4, Week 12, Week 24
Visual Evoked Potential P100 Wave Latency
Mean change from baseline in P100 wave latency, measured by visual evoked potential (VEP), at Week 12, and Week 24. P100 latency is expressed in milliseconds (ms). Longer latency indicates delayed neural conduction and worse visual pathway function; a greater reduction from baseline reflects a better outcome.
Measured: Baseline, Week 12, Week 24
Visual Evoked Potential P100 Wave Amplitude
Mean change from baseline in P100 wave amplitude, measured by visual evoked potential (VEP), at Week 12, and Week 24. P100 amplitude is expressed in microvolts (μV). Higher amplitude indicates better neural signal transmission and visual pathway integrity; a smaller decrease or greater increase from baseline reflects a better outcome.
Measured: Baseline, Week 12, Week 24
Retinal nerve fiber layer (RNFL) thickness
Mean change from baseline in peripapillary retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT), at Week 12 and Week 24. RNFL thickness is expressed in micrometers (μm). Higher values indicate greater structural preservation of the optic nerve; a smaller decrease or greater increase from baseline reflects a better outcome.
Measured: Baseline, Week 12, Week 24,
Ganglion Cell-Inner Plexiform Layer (GCIPL) Thickness
Mean change from baseline in macular ganglion cell-inner plexiform layer (GCIPL) thickness, measured by optical coherence tomography (OCT), at Week 12 and Week 24. GCIPL thickness is expressed in micrometers (μm). Higher values indicate greater structural integrity of the macular ganglion cells; a smaller decrease or greater increase from baseline reflects a better outcome.
Measured: Baseline, Week 12, Week 24
Cross-sectional area of the optic nerve
Mean change from baseline in optic nerve cross-sectional area, measured by magnetic resonance imaging (MRI), at Week 12 and Week 24.
Measured: Baseline, Week 12, Week 24
Length of Optic Nerve Lesion
Mean change from baseline in optic nerve lesion length, measured by magnetic resonance imaging (MRI), at Week 12 and Week 24.
Measured: Baseline, Week 12, Week 24
Concentration of serum sC5b-9
Measured: Baseline, Week 4, Week 12, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2026
- Study start1 Jan 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromyelitis Optica Spectrum Disorders (NMOSD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chao Zhang, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07420296
- Sponsor's protocol ID
- IRB2025-YX-575-01
- Acronym
- ELITE
- Status last verified
- Jan 2026
- First submitted
- 2 Feb 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD sharing is not planned because the informed consent approved by the ethics committee does not include authorization for sharing individual participant data with external researchers.
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modified Zipper Therapy for AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Randomized Controlled Trial Study
- ClinicalTrials.gov ID
- NCT07420296
- Acronym / sponsor ID
- ELITE / IRB2025-YX-575-01
- Keywords
- NMOSD, Eculizumab, Plasma exchange, Corticosteroid pulse therapy, Optic neuritis, Longitudinally extensive transverse myelitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 1 Jan 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 19 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Biological: Eculizumab administration, Drug: High-dose corticosteroid pulse therapy, Procedure: Plasma exchange (PE) |
| Control group | Active comparator | Drug: High-dose corticosteroid pulse therapy, Procedure: Plasma exchange (PE)High-dose corticosteroid pulse therapy+ plasma exchange |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eculizumab administrationComplement 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. | Biological | Experimental group |
| High-dose corticosteroid pulse therapyHigh-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. | Drug | Control group, Experimental group |
| 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. | Procedure or surgery | Control group, Experimental group |
Primary outcome
Best corrected visual acuity
Time frame: Baseline, Week 12
Expanded Disability Status Scale (EDSS)
Time frame: Baseline, Week 12
The Expanded Disability Status Scale (EDSS) is an ordinal scale ranging from 0 to 10, with higher scores indicating worse neurological impairment and disability in patients with neuromyelitis optica spectrum disorder (NMOSD)
10 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Individual participant dataSharing planned: No. IPD sharing is not planned because the informed consent approved by the ethics committee does not include authorization for sharing individual participant data with external researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eculizumab administration, High-dose corticosteroid pulse therapy and Plasma exchange (PE) in people with Neuromyelitis Optica Spectrum Disorders (NMOSD), run by Tianjin Medical University General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chao Zhang (+8602260814587, chaozhang@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best corrected visual acuity (time frame: Baseline, Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.