• A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention

  NCT05269667

  TerminatedInterventionalPhase 4Updated Jan 22, 2025
• A Study to Evaluate the Safety and Efficacy of Satralizumab in Participants With Neuromyelitis Optica Spectrum Disorder (NMOSD)

  NCT04660539

  CompletedInterventionalPhase 3Updated Dec 27, 2024
• Inebilizumab and Rituximab in Neuromyelitis Optica Spectrum Disorders

  NCT06068829

  Unknown statusObservationalUpdated Oct 5, 2023
• An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD

  NCT04201262

  CompletedInterventionalPhase 3Updated Oct 14, 2025
• Safety and Tolerability of Rituximab in Neuromyelitis Optica

  NCT00501748

  CompletedInterventionalPhase 1Updated Sep 27, 2011
• Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Study of Ravulizumab in Chinese Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD)

  NCT07557420

  Not yet recruitingInterventionalPhase 3Updated Jun 18, 2026

ClinicalTrials.gov ID

NCT07010302

Lead Sponsor

Massachusetts General HospitalOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 4

Enrollment

540Estimated

Last Update Posted

Jun 24, 2026Actual

Start Date

Aug 1, 2026Estimated

Primary Completion Date

Jan 2030Estimated

Completion Date

May 2030Estimated

Official Title

A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum Disorder

Brief 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. 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.

• NMOSD

• Rituximab (R)
• Eculizumab (Soliris®)
• Ravulizumab
• Satralizumab
• Inebilizumab

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Double

Lead Sponsor

Massachusetts General HospitalOTHER

Collaborators

Patient-Centered Outcomes Research InstituteOTHER

Charite University, Berlin, GermanyOTHER

The Sumaira FoundationOTHER

friedemann.paul@charite.de+49 30 450 539 705