Multiple Medications for Neuromyelitis Optica Spectrum Disorder

(BEST-NMOSD Trial)

Not yet recruiting at 2 trial locations

Overseen By Anastasia Vishnevetsky, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Disqualifiers: Hepatitis B, Hepatitis C, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which of five medications best prevent relapses in individuals with Neuromyelitis Optica Spectrum Disorder (NMOSD), a condition affecting the eyes and spinal cord, causing symptoms like vision loss and paralysis. Participants will be randomly assigned to receive one of the following medications: rituximab, ravulizumab, inebilizumab, satralizumab, or eculizumab. The trial will compare the effectiveness and safety of these treatments and will also assess disability, patient satisfaction, and quality of life. Adults with NMOSD who test positive for a specific antibody (AQP4-IgG) and can follow the trial procedures are eligible to join. As a Phase 4 trial, the treatments have already received FDA approval and demonstrated effectiveness, helping to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to understand how your current treatments might interact with the trial medications.

What is the safety track record for these treatments?

Research shows that all five medications used in this trial for Neuromyelitis Optica Spectrum Disorder (NMOSD) have undergone safety testing in humans.

1. **Satralizumab**: Studies indicate that satralizumab is generally safe for long-term use in NMOSD patients. It was well-tolerated over an average of four years, maintaining a good safety record.

2. **Complement Inhibitors (Eculizumab and Ravulizumab)**: Research on eculizumab and ravulizumab shows they are safe for NMOSD patients. No major safety issues emerged, even in those who had previously used rituximab.

3. **Inebilizumab**: Studies confirm that inebilizumab is safe for NMOSD patients. However, it should not be used in patients with certain conditions, such as active hepatitis B infection, due to potential risks.

All these treatments have FDA approval for NMOSD, indicating a well-established safety record. Participants in this trial will receive regular monitoring to address any side effects promptly. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study's treatments?

Researchers are excited about these treatments for Neuromyelitis Optica Spectrum Disorder (NMOSD) because they offer new approaches to managing the disease. Eculizumab and Ravulizumab are complement inhibitors that work by blocking a part of the immune system that mistakenly attacks the body, which is different from some standard treatments like Rituximab that target B-cells. Satralizumab and Inebilizumab also bring fresh mechanisms to the table. Satralizumab blocks the interleukin-6 receptor, reducing inflammation, while Inebilizumab targets CD19 on B cells, potentially offering more comprehensive immune modulation. These options could provide patients with additional choices that might be more effective or have different side effect profiles compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for NMOSD?

Research has shown that several treatments can help prevent relapses in people with Neuromyelitis Optica Spectrum Disorder (NMOSD). In this trial, participants may receive Satralizumab, which proved effective, with 96.6% of patients remaining relapse-free over 26 weeks. Another treatment option is Inebilizumab, which maintained about 87.7% of patients free from attacks. Participants may also receive complement inhibitors, such as eculizumab or ravulizumab, which show promise in preventing NMOSD attacks. All these treatments have proven to reduce relapses and are generally safe. These findings assist doctors and patients in choosing the best treatment for NMOSD. ^{1 6 7 8 9}

Who Is on the Research Team?

Philippe-Antoine Bilodeau, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults over 18 with Neuromyelitis Optica Spectrum Disorder (NMOSD) who test positive for AQP4-IgG can join this trial. They must be able to receive the study drugs, follow all procedures, and not be pregnant or planning pregnancy. People with severe allergies to the drugs, certain infections like TB or hepatitis, immunodeficiency disorders, or conditions that could interfere with the study cannot participate.

Inclusion Criteria

I am 18 years old or older.

Eligible to receive any of the study drugs based on clinical judgment

My condition is officially diagnosed as NMOSD.

Exclusion Criteria

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rituximab or one of the four other FDA-approved medications to prevent NMOSD relapses

48 months

Regular assessments including medical exams, surveys, and tests for vision, walking ability, and brain function

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Eculizumab
• Inebilizumab
• Ravulizumab
• Rituximab
• Satralizumab

Trial Overview The trial is testing five medications: Rituximab, Ravulizumab, Inebilizumab, Eculizumab (Soliris®), and Satralizumab in preventing NMOSD relapses. Participants will be randomly assigned a treatment and monitored for effectiveness through medical exams and tests assessing vision, walking ability, brain function as well as patient satisfaction and quality of life.

How Is the Trial Designed?

Group I: Satralizumab Experimental Treatment 1 Intervention

Group II: Open-label, non-randomized Experimental Treatment 5 Interventions

Open-label, non-randomized

Group III: Inebilizumab Experimental Treatment 1 Intervention

Group IV: Complement inhibitors Experimental Treatment 2 Interventions

Ravulizumab or eculizumab

Group V: Rituximab Active Control 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

The Sumaira Foundation

Collaborator

Charite University, Berlin, Germany

Collaborator

Trials

1,071

Recruited

3,739,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.0000000000208776

NMO SPOTLIGHT Registry: Real-World Clinical Outcomes ... Conclusions: Consistent with clinical trial and real-world data previously reported on eculizumab and/or ravulizumab among patients with AQP4- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11963372/

Eculizumab or ravulizumab treatment effect in people with ... See "Long-term safety and effectiveness of eculizumab in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: a 2 ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1645401/full

Eculizumab for the acute attack of neuromyelitis optica ... Conclusion: Eculizumab may yield favorable outcomes in acute NMOSD attacks, with infection monitoring being particularly important in severe cases. Introduction.

4. fcd.mcw.edu fcd.mcw.edu/?search/showPublication/id/2862169

Faculty Collaboration Database - NMO SPOTLIGHT Registry ... NMO SPOTLIGHT Registry: Real-World Clinical Outcomes With Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04201262

NCT04201262 | An Efficacy and Safety Study of ... The primary purpose of this study is to evaluate the efficacy and safety of ravulizumab for the treatment of adult participants with NMOSD.

6. ultomirishcp.com ultomirishcp.com/nmosd

Neuromyelitis optica spectrum disorder (NMOSD) - Ultomiris Safety findings in patients with AQP4+ NMOSD who received eculizumab or ravulizumab in the PREVENT and CHAMPION-NMOSD studies and had received rituximab ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10333632/

Long-term safety and effectiveness of eculizumab in patients ... The objective of the study is to assess the real-world, long-term safety and effectiveness of eculizumab in Japanese patients with AQP4+ NMOSD.

8. neurology.org neurology.org/doi/10.1212/01.wnl.0001051484.02641.a6

Safety Findings in Patients With Anti-Aquaporin-4-Antibody ... No differences in safety were observed among prior-rituximab-treated patients in the PREVENT and CHAMPION-NMOSD studies.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0035378724004764

Disease-modifying treatments for neuromyelitis optica ... Shkrobot, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo ...