Evaluate the superiority of Treatment with RAvulizumab vs plasma exchange during the first episode or a relapse In acute neuromyelitis optica (NMO) patients: a national, multicentric, randomised trial

Ki vehet részt

• Age ≥ 18 years at the time of inclusion
• Female participants of childbearing potential should have no desire to procreate and must agree to use effective contraception throughout the study and for 8 months after the last dose of ravulizumab
• Affiliation to a French social security system
• Patient able to understand the objectives, procedures, and risks associated with the study and able to provide written informed consent
• Patient willing and able to comply with study procedures for the entire study duration
• Diagnosis of neuromyelitis optica spectrum disorder (NMOSD) or isolated acute myelitis and/or optic neuritis with confirmed AQP4-IgG seropositivity, according to the 2015 International Consensus Diagnostic Criteria (Wingerchuk et al., 2015)
• Ongoing acute relapse, defined as new or worsening neurological symptoms occurring within ≤14 days prior to screening
• Incomplete clinical response after 5 consecutive days of intravenous methylprednisolone (5 × 1 g IVMP), assessed at Day 5 and defined at the discretion of the treating neurologist (as per standard practice for escalation to plasma exchange)
• Ravulizumab-naïve patient, defined as no prior exposure to ravulizumab before study enrolment
• The Expanded Disability Status Scale (EDSS) score ≤ 7 at Screening
• Participants who enter the study receiving supportive IST(s) (eg, corticosteroid, azathioprine [AZA], mycophenolate mofetil [MMF], methotrexate [MTX], tacrolimus [TAC], cyclosporin [CsA], or cyclophosphamide [CYC]) for the prevention of relapse, either in combination or monotherapy, must be on a stable dosing regimen of adequate duration prior to Screening, as follows, and remain on a stable dosing regimen during the Screening Period: a. Participants receiving AZA must have been on AZA for ≥ 6 months and have been on a stable dose for ≥ 2 months prior to Screening. b. Participants receiving other IST(s) (eg, MMF, MTX, or TAC) must have been on the IST(s) for ≥ 3 months and have been on a stable dose for ≥ 4 weeks prior to Screening. c. Participants receiving oral corticosteroids must have been on a stable dose for ≥ 4 weeks prior to Screening. d. If a participant has recently discontinued any of the above medications, a period of time equal to the stable dose requirement listed above for that medication (eg, ≥ 2 months for AZA or ≥ 4 weeks for corticosteroids) must have passed prior to the first day of the Screening Period
• For participants who enter the study receiving corticosteroid therapy, the daily dose of corticosteroids must not exceed 0.5 mg/kg/day of prednisone or equivalent and in no case may the dose exceed 20 mg/day
• To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, W 135, and Y within 3 years prior to, or at least 14 days prior to Day 1, according to national/local guidelines. Participants who do not meet this requirement will be vaccinated against meningococcal infection according to national/local guidelines and will receive prophylactic antibiotics for at least 2 weeks after meningococcal vaccination if Day 1 occurs < 2 weeks after initial vaccination

Ki nem vehet részt

• Use of intravenous immunoglobulin (IVIg) or plasma exchange (PE) within 3 weeks prior to Screening
• Active systemic bacterial, viral, or fungal infection within 14 days prior to Day 1
• Previous exposure to ravulizumab
• Previous treatment with plasma exchange upon first appearance of symptoms of the current attack
• Absence of anti-AQP-4 antibodies
• Absence of meningococcal vaccination according to current national recommendations prior to initiation of ravulizumab, unless prophylactic antibiotic coverage is implemented according to guidelines
• Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1
• Known or suspected history of drug or alcohol abuse or dependence (based on current diagnostic and statistical manual of mental disorders, DSM-5) within 2 years prior to Screening
• Use of mitoxantrone within 3 months prior to Screening
• Known hypersensitivity to ravulizumab, murine proteins or any of its excipients
• Visual impairment preventing the participant from signing the informed consent form or completing the questionnaires independently
• History of N meningitidis infection
• History of unexplained, recurrent infection
• Known complement deficiency or history of recurrent meningococcal disease
• Active systemic infection at screening, including unresolved or suspected Neisseria meningitidis infection
• Known to be human immunodeficiency virus (HIV) positive
• Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the participant’s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study
• History of malignancy within 5 years of Screening, with the exception of non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence
• Participation in another interventional clinical trial or receipt of any investigational medicinal product within the legally required exclusion period
• Pregnancy or breastfeeding, or intention to conceive during the study period
• Unable to undergo MRI assessments (e.g., non-compatible implanted device, severe claustrophobia)
• Patient with difficulty to read or understand French and unable to understand study procedures or to provide written informed consent
• Patient under legal protection measure (guardianship, trusteeship, or other court-ordered protection)
• Congenital immunodeficiency