Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD

NCT07010302 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 40200
• Study Type: interventional
• Target: 540
• Locations: 2 countries
• Sites: 3

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.

Conditions

NMOSD

Outcome Measures

Primary Outcomes (2)

• Time to adjudicated safety or tolerability failure

  Includes adverse events, tolerability, patient preference, or logistical barriers.

  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

  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)

  Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months

• Timed 25-Foot Walk

  Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months

• 9-Hole Peg Test

  Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months

• Symbol Digit Modalities Test (SDMT)

  Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months

• Landolt High Contrast Visual Acuity

  Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months

Study Arms (5)

Rituximab

ACTIVE COMPARATOR

Drug: Rituximab (R)

Complement inhibitors

EXPERIMENTAL

Ravulizumab or eculizumab

Drug: Eculizumab (Soliris®); Drug: Ravulizumab

Inebilizumab

EXPERIMENTAL

Drug: Inebilizumab

Satralizumab

EXPERIMENTAL

Drug: Satralizumab

Open-label, non-randomized

OTHER

Open-label, non-randomized

Drug: Rituximab (R); Drug: Eculizumab (Soliris®); Drug: Ravulizumab; Drug: Satralizumab; Drug: Inebilizumab

Interventions

Rituximab (R) DRUG

1000 mg at weeks 0 and 2 followed by 1000 mg every 6 months

Also known as: Rituxan, Truxima

Open-label, non-randomized; Rituximab

Eculizumab (Soliris®) DRUG

900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks

Complement inhibitors; Open-label, non-randomized

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

Complement inhibitors; Open-label, non-randomized

Satralizumab DRUG

120 mg at Weeks 0, 2, 4, followed by 120 mg every 4 weeks

Open-label, non-randomized; Satralizumab

Inebilizumab DRUG

300 mg on Day 1 and Day 15, followed by 300 mg every 6 months

Inebilizumab; Open-label, non-randomized

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Patient-Centered Outcomes Research Institute: collaborator
• Charite University, Berlin, Germany: collaborator
• The Sumaira Foundation: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Related Publications (25)

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MeSH Terms

Interventions

Rituximab; eculizumab; ravulizumab; satralizumab; inebilizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Philippe-Antoine Bilodeau, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe-Antoine Bilodeau, MD

CONTACT

617-726-7565; pbilodeau@mgh.harvard.edu

Anastasia Vishnevetsky, MD

CONTACT

617-726-7565; avishnevetsky@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 8, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

DE (1); US (2)