NMOSDPhase 4BEST-NMOSDNCT07010302
Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD
A Phase 4 study testing Rituximab (R), Eculizumab (Soliris®) and Ravulizumab in people with NMOSD, run by Massachusetts General Hospital at 3 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NMOSD
- What is being tested?
- Rituximab (R), Eculizumab (Soliris®) and Ravulizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Sep 2026to May 2030
- Phase
- Phase 4
- 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
Who may be able to join
- 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.
- Eligible to receive any of the study drugs based on clinical judgment
Who cannot join
- 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.
- Pregnancy or breastfeeding, or intention to conceive during the study period. Pregnancy is excluded due to insufficient safety data for the investigational treatments in this population. Women of childbearing potential must agree to use effective contraception throughout the study and for a defined period following the last dose of study drug, per product labeling or institutional guidance.
- Any medical, psychiatric, or neurological condition that, in the investigator's opinion, may interfere with study participation, pose additional risk to the participant, or confound interpretation of study results.
- Inability or unwillingness to comply with the requirements of the protocol, including scheduled visits, evaluations, or procedures, based on investigator assessment.
- Known hypersensitivity or severe allergic reaction to any component of the study drugs or pre-medications required for infusion.
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
United States2 sites, 2 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Michael Levy, MD, (617) 726-7565, mlevy11@mgh.harvard.edu
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Shamik Bhattacharyya, MD, (617) 726-7565, sbhattacharyya3@bwh.harvard.edu
Germany1 site, 1 recruiting
- Not yet recruiting
Charité - Universitätsmedizin Berlin
Berlin
Friedemann, Paul, +49 30 450 539 705, friedemann.paul@charite.de
About this study
Official title: A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum Disorder
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.
Read more
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.
Read the detailed description
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.
- Conditions
- NMOSD
- Being tested
- Rituximab (R), Eculizumab (Soliris®), Ravulizumab, Satralizumab, Inebilizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (R)Drug
Also called Rituxan, Truxima
1000 mg at weeks 0 and 2 followed by 1000 mg every 6 months
Eculizumab (Soliris®)Drug
900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks
RavulizumabDrug
- 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
SatralizumabDrug
120 mg at Weeks 0, 2, 4, followed by 120 mg every 4 weeks
InebilizumabDrug
300 mg on Day 1 and Day 15, followed by 300 mg every 6 months
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Active comparator | Not described Receives: Drug: Rituximab (R) |
| Complement inhibitors | Experimental | Ravulizumab or eculizumab Receives: Drug: Eculizumab (Soliris®); Drug: Ravulizumab |
| Inebilizumab | Experimental | Not described Receives: Drug: Inebilizumab |
| Satralizumab | Experimental | Not described Receives: Drug: Satralizumab |
| Open-label, non-randomized | Other | Open-label, non-randomized Receives: Drug: Rituximab (R); Drug: Eculizumab (Soliris®); Drug: Ravulizumab; Drug: Satralizumab; Drug: Inebilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to adjudicated safety or tolerability failure
Includes adverse events, tolerability, patient preference, or logistical barriers.
Measured: 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
Measured: From date of randomization until the date of adjudicated relapse or first treatment discontinuation, whichever comes first, assessed up to 48 months
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2025
- Study start1 Sep 2026
- Primary completionJan 2030 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for NMOSDStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, Charite University, Berlin, Germany, The Sumaira Foundation
- Responsible party
- Principal investigator, Philippe A. Bilodeau, MD, Massachusetts General Hospital
- Investigators
- Philippe-Antoine Bilodeau, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07010302
- Sponsor's protocol ID
- 40200
- Acronym
- BEST-NMOSD
- Status last verified
- Sep 2026
- First submitted
- 21 May 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Barreras P, Vasileiou ES, Filippatou AG, Fitzgerald KC, Levy M, Pardo CA, Newsome SD, Mowry EM, Calabresi PA, Sotirchos ES. Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease. Neurology. 2022 Nov 29;99(22):e2504-e2516. doi: 10.1212/WNL.0000000000201260. Epub 2022 Aug 31.
PubMed 36240094Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, von Budingen HC, Kou X, Weber K, Greenberg B. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
PubMed 36007339Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, Drappa J, Katz E. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. Mult Scler. 2022 May;28(6):925-932. doi: 10.1177/13524585211047223. Epub 2021 Oct 1.
PubMed 34595983Kumpfel T, Giglhuber K, Aktas O, Ayzenberg I, Bellmann-Strobl J, Haussler V, Havla J, Hellwig K, Hummert MW, Jarius S, Kleiter I, Klotz L, Krumbholz M, Paul F, Ringelstein M, Ruprecht K, Senel M, Stellmann JP, Bergh FT, Trebst C, Tumani H, Warnke C, Wildemann B, Berthele A; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J Neurol. 2024 Jan;271(1):141-176. doi: 10.1007/s00415-023-11910-z. Epub 2023 Sep 7.
PubMed 37676297Nosadini M, Alper G, Riney CJ, Benson LA, Mohammad SS, Ramanathan S, Nolan M, Appleton R, Leventer RJ, Deiva K, Brilot F, Gorman MP, Waldman AT, Banwell B, Dale RC. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016 Jan 21;3(1):e188. doi: 10.1212/NXI.0000000000000188. eCollection 2016 Feb.
PubMed 26819962Rover C, Friede T. Dynamically borrowing strength from another study through shrinkage estimation. Stat Methods Med Res. 2020 Jan;29(1):293-308. doi: 10.1177/0962280219833079. Epub 2019 Mar 1.
PubMed 30821201Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0000000000001729. Epub 2015 Jun 19.
PubMed 26092914Marcinno A, Marnetto F, Valentino P, Martire S, Balbo A, Drago A, Leto M, Capobianco M, Panzica G, Bertolotto A. Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2018 Sep 13;5(6):e498. doi: 10.1212/NXI.0000000000000498. eCollection 2018 Nov.
PubMed 30258855Clardy SL, Pittock SJ, Aktas O, Nakahara J, Isobe N, Centonze D, Fam S, Kielhorn A, Yu JC, Jansen J, Zhang I. Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder. Neurol Ther. 2024 Jun;13(3):535-549. doi: 10.1007/s40120-024-00597-7. Epub 2024 May 9.
PubMed 38722571Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Nov 28;381(22):2114-2124. doi: 10.1056/NEJMoa1901747.
PubMed 31774956Pittock SJ, Barnett M, Bennett JL, Berthele A, de Seze J, Levy M, Nakashima I, Oreja-Guevara C, Palace J, Paul F, Pozzilli C, Yountz M, Allen K, Mashhoon Y, Kim HJ. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol. 2023 Jun;93(6):1053-1068. doi: 10.1002/ana.26626. Epub 2023 Apr 5.
PubMed 36866852Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-625. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3.
PubMed 31050279Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, Fukaura H, Nomura K, Shimizu Y, Mori M, Nakashima I, Misu T, Umemura A, Yamamoto K, Sawada H. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Apr;19(4):298-306. doi: 10.1016/S1474-4422(20)30066-1. Epub 2020 Mar 18.
PubMed 32199095Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.
PubMed 23897062Kleiter I, Gold R. Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders. Neurotherapeutics. 2016 Jan;13(1):70-83. doi: 10.1007/s13311-015-0400-8.
PubMed 26597098
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum Disorder
- ClinicalTrials.gov ID
- NCT07010302
- Acronym / sponsor ID
- BEST-NMOSD / 40200
- Conditions
- NMOSD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, Charite University, Berlin, Germany, The Sumaira Foundation
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- May 2030 (estimated)
- First posted
- 8 Jun 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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Active comparator | Drug: Rituximab (R) |
| Complement inhibitors | Experimental | Drug: Eculizumab (Soliris®), Drug: RavulizumabRavulizumab or eculizumab |
| Inebilizumab | Experimental | Drug: Inebilizumab |
| Satralizumab | Experimental | Drug: Satralizumab |
| Open-label, non-randomized | Other | Drug: Rituximab (R), Drug: Eculizumab (Soliris®), Drug: Ravulizumab, Drug: Satralizumab, Drug: InebilizumabOpen-label, non-randomized |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- Eligible to receive any of the study drugs based on clinical judgment
Key exclusion criteria (8 listed)
- 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.
- Pregnancy or breastfeeding, or intention to conceive during the study period. Pregnancy is excluded due to insufficient safety data for the investigational treatments in this population. Women of childbearing potential must agree to use effective contraception throughout the study and for a defined period following the last dose of study drug, per product labeling or institutional guidance.
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 |
|---|---|---|
| Rituximab (R)Also: Rituxan, Truxima1000 mg at weeks 0 and 2 followed by 1000 mg every 6 months | Drug | Open-label, non-randomized, Rituximab |
| Eculizumab (Soliris®)900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks | Drug | Complement inhibitors, Open-label, non-randomized |
| Ravulizumab* 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 | Drug | Complement inhibitors, Open-label, non-randomized |
| Satralizumab120 mg at Weeks 0, 2, 4, followed by 120 mg every 4 weeks | Drug | Open-label, non-randomized, Satralizumab |
| Inebilizumab300 mg on Day 1 and Day 15, followed by 300 mg every 6 months | Drug | Inebilizumab, Open-label, non-randomized |
Primary outcome
Time to adjudicated safety or tolerability failure
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
Includes adverse events, tolerability, patient preference, or logistical barriers.
Time to adjudicated relapse
Time frame: From date of randomization until the date of adjudicated relapse or first treatment discontinuation, whichever comes first, assessed up to 48 months
As determined by the blinded Relapse Adjudication Committee using pre-specified clinical and imaging criteria
12 secondary outcomes
Expanded Disability Status Scale (EDSS)
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
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
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)
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
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
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)
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)
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
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
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
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
Brief Pain Inventory
Time frame: Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months
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 24 Sep 2026.
- Background: PubMed 36240094Barreras P, Vasileiou ES, Filippatou AG, Fitzgerald KC, Levy M, Pardo CA, Newsome SD, Mowry EM, Calabresi PA, Sotirchos ES. Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease. Neurology. 2022 Nov 29;99(22):e2504-e2516. doi: 10.1212/WNL.0000000000201260. Epub 2022 Aug 31.
- Background: PubMed 36007339Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, von Budingen HC, Kou X, Weber K, Greenberg B. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
- Background: PubMed 34595983Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, Drappa J, Katz E. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. Mult Scler. 2022 May;28(6):925-932. doi: 10.1177/13524585211047223. Epub 2021 Oct 1.
- Background: PubMed 37676297Kumpfel T, Giglhuber K, Aktas O, Ayzenberg I, Bellmann-Strobl J, Haussler V, Havla J, Hellwig K, Hummert MW, Jarius S, Kleiter I, Klotz L, Krumbholz M, Paul F, Ringelstein M, Ruprecht K, Senel M, Stellmann JP, Bergh FT, Trebst C, Tumani H, Warnke C, Wildemann B, Berthele A; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J Neurol. 2024 Jan;271(1):141-176. doi: 10.1007/s00415-023-11910-z. Epub 2023 Sep 7.
- Background: PubMed 26819962Nosadini M, Alper G, Riney CJ, Benson LA, Mohammad SS, Ramanathan S, Nolan M, Appleton R, Leventer RJ, Deiva K, Brilot F, Gorman MP, Waldman AT, Banwell B, Dale RC. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016 Jan 21;3(1):e188. doi: 10.1212/NXI.0000000000000188. eCollection 2016 Feb.
- Background: PubMed 30821201Rover C, Friede T. Dynamically borrowing strength from another study through shrinkage estimation. Stat Methods Med Res. 2020 Jan;29(1):293-308. doi: 10.1177/0962280219833079. Epub 2019 Mar 1.
- Background: PubMed 26092914Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0000000000001729. Epub 2015 Jun 19.
- Background: PubMed 30258855Marcinno A, Marnetto F, Valentino P, Martire S, Balbo A, Drago A, Leto M, Capobianco M, Panzica G, Bertolotto A. Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2018 Sep 13;5(6):e498. doi: 10.1212/NXI.0000000000000498. eCollection 2018 Nov.
- Background: PubMed 38722571Clardy SL, Pittock SJ, Aktas O, Nakahara J, Isobe N, Centonze D, Fam S, Kielhorn A, Yu JC, Jansen J, Zhang I. Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder. Neurol Ther. 2024 Jun;13(3):535-549. doi: 10.1007/s40120-024-00597-7. Epub 2024 May 9.
- Background: PubMed 31774956Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Nov 28;381(22):2114-2124. doi: 10.1056/NEJMoa1901747.
- Background: PubMed 36866852Pittock SJ, Barnett M, Bennett JL, Berthele A, de Seze J, Levy M, Nakashima I, Oreja-Guevara C, Palace J, Paul F, Pozzilli C, Yountz M, Allen K, Mashhoon Y, Kim HJ. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol. 2023 Jun;93(6):1053-1068. doi: 10.1002/ana.26626. Epub 2023 Apr 5.
- Background: PubMed 31050279Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-625. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3.
- Individual participant dataSharing planned: Undecided
Related trials for NMOSD
Recruiting
Impact of a Structured Wellness Behavioral Intervention on Quality of Life in NMOSD
Neuromyelitis Optica Spectrum Disorder (NMOSD)
RecruitingObservational study
Observational Safety Study in Women With Neuromyelitis Optica Spectrum Disorder (NMOSD) Exposed to UPLIZNA® During Pregnancy
Neuromyelitis Optica Spectrum Disorder, Pregnancy Related
RecruitingPhase 2
Efgartigimod for the Treatment of Acute Optic Neuritis
Optic Neuritis
Not yet recruitingPhase 1/2
A Safety and Efficacy Study Evaluating CTX112 in Subjects With Refractory Neurologic Autoimmune Disease
Progressive Multiple Sclerosis (PMS), Neuromyelitis Optica
RecruitingObservational study
Registry of Patients With AQP4+ NMOSD Treated With Alexion C5 Inhibitor Therapies
Neuromyelitis Optica Spectrum Disorder, NMOSD
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.
Philippe-Antoine Bilodeau, MD principal investigator
Massachusetts General Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rituximab (R), Eculizumab (Soliris®) and Ravulizumab in people with NMOSD, run by Massachusetts General Hospital at 3 sites in 2 countries.
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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Germany. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Philippe-Antoine Bilodeau, MD (617-726-7565, pbilodeau@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to adjudicated safety or tolerability failure (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07010302, which also lists 25 linked publications.
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 24 Sep 2026.