Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD
ConditionNMOSD
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorMassachusetts General Hospital
About this trial
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune condition that mainly affects the eyes and spinal cord, causing serious symptoms such as vision loss, paralysis, and severe pain. This trial compares the effectiveness and safety of five medications commonly used to prevent NMOSD relapses: rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab.
In this study, 160 adults with NMOSD who test positive for a specific antibody (AQP4-IgG) will participate. They will be randomly assigned to receive either rituximab or one of the four other FDA-approved medications. The main goal is to find out which treatment best prevents relapses and has fewer serious side effects. The trial will also measure disability, patient satisfaction, quality of life, and biomarkers that help track disease activity.
Participants will have regular assessments, including medical exams, surveys, and tests for vision, walking ability, and brain function. They will report any side effects or health issues experienced during the study. The trial will last from one to four years for each participant.
This research aims to help patients and doctors make better-informed treatment decisions by providing clear evidence about the best available therapies for NMOSD.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of NMOSD according to the 2015 International Panel for NMO Diagnosis (IPND) consensus criteria.
Seropositivity for AQP4 immunoglobulin G (AQP4-IgG) confirmed by a cell-based assay (either live or fixed) that meets the threshold for positivity set by the local testing laboratory.
Age ≥18 years at the time of consent.
Ability and willingness to provide informed consent and comply with all study procedures, including scheduled visits, laboratory tests, and assessments.
Disqualifiers
Known active hepatitis B virus (HBV) infection, defined as a positive hepatitis B surface antigen or detectable HBV DNA by PCR.
Known active hepatitis C virus (HCV) infection, defined as detectable HCV RNA by PCR.
Known active or latent tuberculosis, evidenced by a positive interferon-gamma release assay (IGRA) unless fully treated per local guidelines before enrollment.
Known or suspected immunodeficiency disorders, including but not limited to HIV infection with CD4 count <200 cells/mm³ or any condition requiring chronic immunosuppressive therapy outside the scope of the study drugs.
Trial design
Design model
Parallel
Treatments tested in this trial
Rituximab (R)
Drug1000 mg at weeks 0 and 2 followed by 1000 mg every 6 months
Eculizumab (Soliris®)
Drug900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks
Ravulizumab
Drug* 40 to \< 60 kg: 2400 mg * 60 to \< 100 kg: 2700 mg * 100 kg: 3000 mg as an induction dose, followed by * 40 to \< 60 kg: 3000 mg * 60 to \< 100 kg: 3300 mg * 100 kg: 3600 mg Every 8 weeks starting 15 days after loading dose
Satralizumab
Drug120 mg at Weeks 0, 2, 4, followed by 120 mg every 4 weeks
Inebilizumab
Drug300 mg on Day 1 and Day 15, followed by 300 mg every 6 months
Treatment groups
540 Participants
are divided into 5 treatment groupsGroup A: RituximabActive comparator 1 intervention
Group B: Complement inhibitorsExperimental treatment 2 interventions
Group C: InebilizumabExperimental treatment 1 intervention
Group D: SatralizumabExperimental treatment 1 intervention
Group E: Open-label, non-randomizedOther 5 interventions
Trial outcomes
Primary outcomes
1
Time to adjudicated safety or tolerability failure
Includes adverse events, tolerability, patient preference, or logistical barriers.
Time frame
From date of randomization until the date of first adjudicated safety or tolerability failure or adjudicated relapse, whichever comes first, assessed up to 48 months2
Time to adjudicated relapse
As determined by the blinded Relapse Adjudication Committee using pre-specified clinical and imaging criteria
Time frame
From date of randomization until the date of adjudicated relapse or first treatment discontinuation, whichever comes first, assessed up to 48 monthsSecondary outcomes
1
Expanded Disability Status Scale (EDSS)
Quantifies the severity of disability in patients with neuroinflammatory disorders such as NMOSD. The scale ranges from 0 to 10 in half-point increments, where 0 indicates normal neurological function and 10 represents death due to neurological causes. Higher scores reflect greater disability.
Time frame
Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months2
Timed 25-Foot Walk
Measures ambulatory function. Participants are instructed to walk 25 feet as quickly and safely as possible. The time to complete the walk is recorded; lower times indicate better function.
Time frame
Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months3
9-Hole Peg Test
Assesses upper extremity function and fine motor coordination. Participants place and remove nine pegs into a pegboard as quickly as possible using one hand. The test is performed separately for each hand. The time to complete the task is recorded; shorter times reflect better performance.
Time frame
Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months4
Symbol Digit Modalities Test (SDMT)
Evaluates cognitive processing speed. Participants are presented with a series of symbols matched with numbers and asked to substitute the corresponding number for each symbol within 90 seconds. The total number of correct responses is recorded; higher scores indicate better cognitive performance.
Time frame
Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 monthsSponsors and contacts
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Massachusetts General Hospital
Lead sponsor
Patient-Centered Outcomes Research Institute
Collaborator
Charite University, Berlin, Germany
Collaborator
The Sumaira Foundation
Collaborator
Source ClinicalTrials.gov