NMOSDNCT06903130
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)
An observational study of NMOSD, run by National and Kapodistrian University of Athens at 1 site in Greece.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NMOSD
- What is being tested?
- Blood samples for sNfL and sGFAP levels
- How many people
- 40 participants
- Where
- 1 siteGreece
- Study dates
- 1 Sep 2025to 1 Jun 2028
- How long will I take part?
- 24 Months
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- 7. Use of satralizumab within 3 months prior to Enrollment. 8. Pregnant, breastfeeding, or intending to conceive during the course of the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Greece1 site
Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens
Athens, 12462
Georgios Tsivgoulis, +302105832471, gtsivou@med.uoa.gr
About this study
Official title: An Exploratory, Non-Interventional, Prospective, Multicenter, Nationwide, 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)
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
Read the 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:
- Measurement of sNfL levels.
- Measurement of sGFAP levels.
- Clinical assessment: neurological examination/disability evaluation based on the EDSS.
- 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.
- Conditions
- NMOSD
- Being tested
- Blood samples for sNfL and sGFAP levels
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samples for sNfL and sGFAP levelsDiagnostic test
Blood samples for sNfL and sGFAP levels
| Study group | Role | What they receive |
|---|---|---|
| AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment | AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment with Ravulizumab (group A) Receives: 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) Receives: Diagnostic Test: Blood samples for sNfL and sGFAP levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
• 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
Measured: 2 years
Secondary outcomes (1)
Correlation analysis of sGFAP and sNfL levels with the EDSS score.
To evaluate the association of sGFAP and sNfL levels with clinical disability.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2025
- Study start1 Sep 2025 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NMOSDStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgios Tsivgoulis, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06903130
- Sponsor's protocol ID
- ESR-24-22351
- Status last verified
- Jun 2025
- First submitted
- 24 Mar 2025
- Last updated
- 1 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Non-Interventional, Prospective, Multicenter, Nationwide, 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)
- ClinicalTrials.gov ID
- NCT06903130
- Acronym / sponsor ID
- ESR-24-22351
- Conditions
- NMOSD
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 30 Mar 2025 (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.
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:
- Measurement of sNfL levels.
- Measurement of sGFAP levels.
- Clinical assessment: neurological examination/disability evaluation based on the EDSS.
- 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 design
- Observational model
- Other
- Time perspective
- Prospective
- Target follow-up
- 24 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment | – | Diagnostic Test: Blood samples for sNfL and sGFAP levelsAQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment with Ravulizumab (group A) |
| AQP4-IgG seropositive NMOSD patients receiving off-label ISTs | – | Diagnostic Test: Blood samples for sNfL and sGFAP levelsAQP4-IgG seropositive NMOSD patients receiving off-label ISTs including rituximab, corticosteroids, azathioprine, and mycophenolate mofetil (group B) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
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 |
|---|---|---|
| Blood samples for sNfL and sGFAP levelsBlood samples for sNfL and sGFAP levels | Diagnostic test | AQP4-IgG seropositive NMOSD patients receiving complement inhibitor treatment, AQP4-IgG seropositive NMOSD patients receiving off-label ISTs |
Primary outcome
• Changes in sNfL and sGFAP levels during disease course in AQP4-IgG NMOSD seropositive patients receiving Ravulizumab
Time frame: 2 years
To evaluate sNfL and sGFAP levels and their fluctuations over time in AQP4-IgG seropositive NMOSD patients receiving complement inhibitor Ravulizumab
1 secondary outcome
Correlation analysis of sGFAP and sNfL levels with the EDSS score.
Time frame: 2 years
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 1 Jul 2025.
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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.
Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens
Athens, Greece
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NMOSD, run by National and Kapodistrian University of Athens at 1 site in Greece.
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 14 inclusion and 11 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: opening soon, as of the sponsor's last update on 1 Jul 2025. 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 Greece. 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.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Changes in sNfL and sGFAP levels during disease course in AQP4-IgG NMOSD seropositive patients receiving Ravulizumab (time frame: 2 years). 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 1 Jul 2025.