Efficacy, Safety, PK, PD, and ADA of Eculizumab in Chinese Adults With NMOSD (ECU-NMO-304)

An Open-label, Single-arm, Multi-Center, Interventional Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Chinese Adult Participants With Anti-Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders (NMOSD)

The primary objective of this study is to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of Eculizumab in Chinese Adults with Neuromyelitis Optica Spectrum Disorders (NMOSD).

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromyelitis Optica Spectrum Disorders; NMOSD
• Intervention / Treatment: Drug: eculizumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100016
    • Research Site
  • Dongguan, China, 523059
    • Research Site
  • Jinan, China, 250012
    • Research Site
  • Shanghai, China, 200040
    • Research Site
  • Taiyuan, China, 030001
    • Research Site
  • Wenzhou, China, 325000
    • Research Site
  • Wuhan, China, 430030
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria
• Anti-AQP4 antibody positive
• At least 1 attack or relapse in the last 12 months prior to the Screening Period
• EDSS score ≤ 7
• If a participant enters the study receiving IST(s) for relapse prevention, the participant must be on a stable maintenance dose of IST(s) as follows, prior to screening and must remain on that dose for the duration of the study, unless the participant experiences a relapse
• Female participants of childbearing potential must have a negative pregnancy test (serum HCG at screening

• Male participants are eligible to participate if they agree to the following during the study intervention Treatment Period and for at least 5 months after the last dose of study intervention:

  • Refrain from donating fresh unwashed semen. PLUS, either,
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR

  • Must agree to use barrier as detailed below:

    • Agree to use a male condom when having sexual intercourse with a WOCBP who is not currently pregnant.

Exclusion Criteria:

• Pregnant, breastfeeding, or intending to conceive during the course of the study
• Prior history of N meningitidis infection or unresolved meningococcal disease
• Any systemic bacterial or other infection which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics
• Presence of fever ≥ 38 C within 7 days prior to study intervention administration on Day 1
• Hypersensitivity to murine proteins or to one of the excipients of study intervention
• Use of rituximab, inebilizumab, or other B cell-depleting therapy within 6 months prior to Day 1 and during the study
• Use of mitoxantrone or satralizumab within 3 months prior to screening and during the study
• Use of IVIg within 3 weeks prior to screening
• If a participant enters the study receiving oral corticosteroid(s) with or without other ISTs, the daily corticosteroid dose must be no more than prednisone 20 mg/day (or equivalent) prior to screening and the participant must remain on that dose for the duration of the study or until the participant experiences a relapse (specific medications listed in Section 6.9.1 may be allowed)
• Has previously received treatment with C5 inhibitors
• Participation in any other investigational drug study or exposure to an investigational drug or device within 5 half-lives of treatment (if known) or 30 days, which is longer, before the first dose administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eculizumab; All participants will receive open-label eculizumab by intravenous infusion during the Treatment Period, starting on Day 1 for a total of up to 52 weeks.	Drug: eculizumab; Participants will receive eculizumab by intravenous (IV) infusion for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of eculizumab in anti-AQP4 antibody positive participants with NMOSD measured by Adjudicated On-trial annualized relapse rate (ARR).	The mean (95% Confidence Interval) of patient-level Adjudicated On-trial annualized relapse rate (ARR)	Baseline through Week 52
The efficacy of eculizumab in anti-AQP4 antibody positive participants with NMOSD measured by Adjudicated On-trial annualized relapse rate (ARR).	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicine	Baseline through Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of eculizumab by assessing change from baseline to end of study in Expanded Disability Status Scale (EDSS) Score	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: The mean (95% Confidence Interval) change from baseline to end of study in EDSS score	Baseline through Week 52
The efficacy of eculizumab by assessing change from baseline to end of study in Ambulatory Function as Measured by Hauser Ambulation Index (HAI)	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: The mean (95% Confidence Interval) change from baseline to end of study in ambulatory function as measured by Hauser ambulation index (HAI)	Baseline through Week 52
The efficacy of eculizumab by assessing change from baseline to end of study in European Quality of Life 5-Dimension Questionnaire (EQ-5D) Index Score	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: The mean (95% Confidence Interval) change from baseline to end of study in EQ-5D index score	Baseline through Week 52
Change From Baseline to end of study in EQ-5D Visual Analogue Scale (VAS) Score	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: The mean (95% Confidence Interval) change from baseline to end of study in EQ-5D VAS	Baseline through Week 52
Serum Eculizumab Concentrations Over Time	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: Mean serum eculizumab concentrations at all scheduled visits	Baseline through Week 52
Serum Free Complement Component 5 (C5) Concentrations Over Time	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: Mean changes in serum free C5 concentrations at all scheduled visits	Baseline through Week 52
Number of Treatment-emergent Antidrug Antibody (ADA) Positive Participants	Intercurrent Event (ICE): ICE1: Premature discontinuation of study intervention; ICE2: Initiation of disallowed therapy or medicineSummary measure: Proportion of treatment-emergent ADA positive participants	Baseline through Week 52
To characterize the overall safety of eculizumab in the treatment of NMOSD	Number of participants with TEAEs, SAEs, and TEAEs leading to study intervention discontinuation, with abnormal vital signs, abnormal ECG readings, and abnormal laboratory tests results	Baseline through Week 52

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Xiangjun Chen, M.D, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2025
• Primary Completion (Estimated): December 7, 2026
• Study Completion (Estimated): December 7, 2026

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: eculizumab; Neuromyelitis Optica Spectrum Disorders; anti-AQP4; NMOSD
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; eculizumab
• Other Study ID Numbers: D7412C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No