A Phase 4 interventional study of Rituximab (R) and Eculizumab (Soliris®) in NMOSD, sponsored by Massachusetts General Hospital. Recruiting at 3 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Treatment
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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.
Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune inflammatory disorder primarily affecting the optic nerves and spinal cord, leading to symptoms such as blindness, severe muscle weakness, paralysis, and significant pain. This study aims to directly compare the clinical effectiveness and safety profiles of five distinct therapies widely utilized to prevent disease relapses in patients with NMOSD who test positive for aquaporin-4 antibodies (AQP4-IgG): rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab.
The study is designed as an international, multicenter, randomized, adaptive clinical trial. It involves enrolling 160 adult participants diagnosed with AQP4-IgG positive NMOSD, who will be randomized in equal numbers to receive either rituximab or one of the four other FDA-approved therapies-ravulizumab, inebilizumab, satralizumab, or eculizumab. Patients randomized to the non-rituximab group will undergo further randomization into one of these four comparator medications. Additionally, the study incorporates an observational cohort for patients who decline randomization but agree to be followed according to the same protocol.
The primary objective is to evaluate the comparative effectiveness of rituximab versus the other treatments in preventing NMOSD relapses and treatment failure due to adverse events. Secondary objectives include comparing disability outcomes, evaluating treatment-related adverse events, and assessing impacts on patient-reported quality of life, as well as examining changes in biomarkers relevant to NMOSD disease activity.
Participants will undergo comprehensive evaluations at regular intervals, including detailed neurological examinations, standardized functional assessments (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC]), visual acuity and contrast sensitivity testing, and cognitive assessments. Additionally, patient-reported outcomes such as fatigue, pain, mental health status, and overall quality of life will be collected systematically through validated surveys. Safety assessments will include regular monitoring of blood work, clinical evaluations for infections and other complications, and documentation of all adverse events.
Advanced exploratory analyses will also include biomarker studies involving optical coherence tomography (OCT) to assess retinal nerve fiber layer loss, and assays for serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels. The study will track direct and indirect healthcare costs, as well as impacts on employment and caregiver burden.
The duration of participation will range from one to four years, depending on when participants enroll and their clinical outcomes. All data will be rigorously analyzed using advanced statistical methods, including time-to-event analyses, mixed-effects models, and Bayesian hierarchical approaches to allow robust comparative effectiveness evaluations.
Ultimately, this research aims to provide high-quality, head-to-head data to inform clinical decision-making, optimize treatment strategies, and improve patient outcomes for those living with NMOSD.
Massachusetts General Hospital is the lead sponsor of 2,589 studies on the registry; 447 are open to participants now.
Of its 223 completed or terminated interventional studies of FDA-regulated products, 168 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Rituximab (R)
Ravulizumab or eculizumab
Drug: Eculizumab (Soliris®) · Drug: Ravulizumab
Drug: Inebilizumab
Drug: Satralizumab
Open-label, non-randomized
Drug: Rituximab (R) · Drug: Eculizumab (Soliris®) · Drug: Ravulizumab · Drug: Satralizumab · Drug: Inebilizumab
1000 mg at weeks 0 and 2 followed by 1000 mg every 6 months
Also known as: Rituxan, Truxima
900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks
* 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
120 mg at Weeks 0, 2, 4, followed by 120 mg every 4 weeks
300 mg on Day 1 and Day 15, followed by 300 mg every 6 months
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 months
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 months
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 months
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 months
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 months
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 months
Landolt High Contrast Visual Acuity
Assessed using Landolt ring optotypes under standard lighting conditions. Participants identify the orientation of the ring (gap in one of four cardinal directions). The number of correct responses is converted to a visual
Time frame: Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months
Landolt Low Contrast Visual Acuity
Assessed using Landolt ring optotypes at 2.5% contrast. Participants identify the orientation of the ring (gap in one of four cardinal directions). The number of correct responses is converted to a visual acuity ratio (Snellen equivalent). Higher ratios indicate better low contrast vision.
Time frame: Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months
Treatment Satisfaction Questionnaire for Medication II (TSQM-II)
Assesses patient satisfaction with medication across multiple domains, including effectiveness, side effects, convenience, and global satisfaction. Higher scores indicate greater satisfaction with treatment.
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
EuroQol 5-Dimension 5-Level (EQ-5D-5L)
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression . Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Index values, calculated using country-specific value sets, range from less than 0 (health states considered worse than death) to 1 (full health). An associated visual analog scale (VAS) records the respondent's self-rated health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
PROMIS Depression Short form
8-item self-report questionnaire used to assess depression
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Fatigue Scale for Motor and Cognitive Function
20-item patient-reported measure assessing both motor and cognitive fatigue in individuals with neuroinflammatory diseases. It yields separate subscale scores and a total fatigue score; higher scores indicate greater fatigue.
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Visual Function Questionnaire 25
Neasures vision-related quality of life across 12 subscales, including general vision, ocular pain, and social functioning. It is designed for individuals with chronic eye diseases. Higher scores indicate better self-reported visual function.
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Brief Pain Inventory
Evaluates pain severity and the impact of pain on daily functions. It includes both numeric rating scales and interference items related to activity, mood, walking, and sleep. Higher scores on severity and interference scales indicate more severe and impactful pain.
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Plan to share: Undecided
Started Sep 2026 (actual). Primary completion is estimated for Jan 2030, 40 months after the start.
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Studies of the drugs tested here: Eculizumab · Ravulizumab · Satralizumab · Inebilizumab
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