Clinical Study to Evaluate the Effects of the Complement C5 Inhibitor Ravulizumab on Serum Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) Levels in Patients with Aquaporin-4-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Not yet recruiting

• Conditions: NMOSD

• Registration Number: NCT06903130
• Lead Sponsor: National and Kapodistrian University of Athens

Brief Summary

This is a nationwide observational study looking at how ravulizumab, a complement C5 inhibitor, affects blood biomarkers o sNfL and sGFAP in people with AQP4-antibody positive NMOSD. The study does not change your treatment-only regular blood samples are collected to monitor these markers

Detailed Description

This is an exploratory, non-interventional, prospective, multicenter, clinical study. The maximum total number of 40 patients with a diagnosis of seropositive AQP4-IgG NMOSD is expected to be enrolled. The goal is to include at least one-third of these patients in the complement inhibitor ravulizumab group, with the remaining patients in the off-label ISTs group based on current therapeutic clinical practice in Greece. Multiple Neurological Departments with experience in NMOSD diagnosis and treatment will participate. Eligible patients will be recruited in both groups and each participant will be followed up approximately every 60 days for 24 months.

Data Source(s):

Study-related data will be collected and recorded at specific and predetermined data collection timepoints, during routine clinical and laboratory assessments. Information related to the patients' medical history will be collected for the NMOSD patients from each neurological department's database (records/files/electronic database) and patient self-reports. Baseline characteristics (age, sex, height, body weight, and BMI) will also be recorded for all participants.

Study Population:

The target population in the study will include diagnosed patients with AQP4-IgG seropositive NMOSD. Age ≥ 18 years with a history of ≥ 1 NMOSD clinical attack according to 2015 NMOSD criteria. The participants should be undergoing treatment either with off-label ISTs (corticosteroids, azathioprine, mycophenolate mofetil, rituximab) or complement inhibitor therapy with ravulizumab. Corticosteroids can be used as add-on therapy to ravulizumab or the off-label ISTs

Procedures:

1. Measurement of sNfL levels.

2. Measurement of sGFAP levels.

3. Clinical assessment: neurological examination/disability evaluation based on the EDSS.

4. Brain/spinal cord MRI: the number, size, anatomical location of lesions will be assessed. Gadolinium enhancement will also be evaluated whenever post-gadolinium T1-weighted MRI images are available.

* Scheduled serum collection time points for biomarker measurements (sGFAP, sNfL) and clinical assessments: at the first data recording at Visit 1 and subsequently every 60 (±15) days during the follow-up period, which is set at 24 months.

* Interim timepoints related to clinical episodes for serum collection of biomarker measurements (sGFAP, sNfL) and clinical assessments: at the onset of a clinical episode (48-hours window).

* All participants will be clinically evaluated during scheduled follow-ups for sample acquisition or during attack-related visits; clinical evaluation will include neurological examination, MRI evaluation whenever applicable, clinical disability assessment by the EDSS and routine blood test assessment.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-24
• Study First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-30
• Last Update Posted: 2025-03-30
• Study Start: 2025-05-01
• Primary Completion: 2027-12-01
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
• Changes in sNfL and sGFAP levels during disease course in AQP4-IgG NMOSD seropositive patients receiving Ravulizumab	2 years	To evaluate sNfL and sGFAP levels and their fluctuations over time in AQP4-IgG seropositive NMOSD patients receiving complement inhibitor Ravulizumab

Secondary Outcome Measures

Name	Time	Method
Correlation analysis of sGFAP and sNfL levels with the EDSS score.	2 years	To evaluate the association of sGFAP and sNfL levels with clinical disability.

Trial Locations

Locations (1)

Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens; 🇬🇷 Athens, Greece