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)

NCT06903130 | Not Yet Recruiting

• 1 other identifier: ESR-24-22351
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

NMOSD

Outcome Measures

Primary Outcomes (1)

• • Changes in sNfL and sGFAP levels during disease course in AQP4-IgG NMOSD seropositive patients receiving Ravulizumab

  To evaluate sNfL and sGFAP levels and their fluctuations over time in AQP4-IgG seropositive NMOSD patients receiving complement inhibitor Ravulizumab

  2 years

Secondary Outcomes (1)

• Correlation analysis of sGFAP and sNfL levels with the EDSS score.

  2 years

Other Outcomes (2)

• Changes in sGFAP levels in patients experiencing relapse

  2 years

• Alterations in sNfL and sGFAP levels during disease course in AQP4-IgG NMOSD seropositive patients receiving receiving off-label ISTs

  2 years

Study Arms (2)

AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment

AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment with Ravulizumab (group A)

Diagnostic Test: Blood samples for sNfL and sGFAP levels

AQP4-IgG seropositive NMOSD patients receiving off-label ISTs

AQP4-IgG seropositive NMOSD patients receiving off-label ISTs including rituximab, corticosteroids, azathioprine, and mycophenolate mofetil (group B)

Diagnostic Test: Blood samples for sNfL and sGFAP levels

Interventions

Blood samples for sNfL and sGFAP levels DIAGNOSTIC_TEST

Blood samples for sNfL and sGFAP levels

AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment; AQP4-IgG seropositive NMOSD patients receiving off-label ISTs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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 criteria1. 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.

You may qualify if:

• Patients are eligible to be included in the study only if all of the following criteria apply:
• Age
• Patient must be 18 years of age or older, at the time of signing the informed consent.
• Type of Patient and Disease Characteristics
• Anti-AQP4 Ab-positive at screening and a diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria (Wingerchuk, 2015). A historically positive anti-AQP4 Ab test may be acceptable if the test was performed using an acceptable, validated cell-based assay from an accredited laboratory.
• At least 1 clinical attack prior to the Prescreening/Screening Periods.
• Treatment-naïve patients or patients under specific off-label treatments (rituximab, corticosteroids, azathioprine, mycophenolate mofetil) or the complement C5 inhibitor ravulizumab. Naïve patients who initiate ravulizumab at enrolment, should have been prescribed ravulizumab, but not yet initiated treatment, according to the label and local market reimbursement criteria.
• Vaccinated against N. meningitidis (for serogroups A, C, W, Y and B) a) within 3 years and at least 2 weeks prior to the first dose of ravulizumab, or b) at the time of the first dose of ravulizumab provided that antibacterial drug prophylaxis is administered as per National Vaccination Guidelines and Summary of Product Characteristics of ravulizumab.
• Weight
• Body weight ≥ 40 kg.
• Sex
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those receiving each immunotherapy.
• Informed Consent
• Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• Medical Conditions
• History of N. meningitidis infection.
• Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer)
• History of unexplained infections.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to screening.
• Presence of fever ≥ 38°C (100.4°F) within 7 days prior to screening
• NMOSD pregnant women will be excluded according to the local clinical practice. '
• History of implanted medical devices which are incompatible with strong magnetic fields used for MRI.
• Prior/Concomitant Therapy 6. Use of inebilizumab within 6 months prior to Enrollment in patients switching to another therapy i.e. ravulizumab or the off-label ISTs.
• \. Use of satralizumab within 3 months prior to Enrollment. 8. Pregnant, breastfeeding, or intending to conceive during the course of the study

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead

Study Sites (1)

Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens

Athens, 12462, Greece

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples for sNfL and sGFAP levels

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Chairman of Second Department of Neurology, School of Medicine, National & Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Locations

GR (1)