Ravulizumab for Neuromyelitis Optica Spectrum Disorders

Recruiting at 31 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Alexion Pharmaceuticals

Must be taking: Eculizumab

Must not be taking: Rituximab, Biologics, IVIg

Disqualifiers: Multiple sclerosis, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a medication called ravulizumab (Ultomiris) for children with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD causes inflammation in the nerves of the eyes and spinal cord. Participants will receive ravulizumab through an IV for up to 154 weeks. The trial seeks children with NMOSD who test positive for a specific antibody and have experienced at least one attack or relapse in the past year. As a Phase 2/3 trial, it aims to assess the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering hope for effective treatment.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications, but you need to be on a stable dose of any supportive medications you are already taking. However, you cannot have used rituximab within 6 months or certain other treatments close to the trial start.

Is there any evidence suggesting that ravulizumab is likely to be safe for humans?

Research has shown that ravulizumab, also known as ULTOMIRIS, is generally well-tolerated by people with Neuromyelitis Optica Spectrum Disorder (NMOSD). In one study, participants taking ravulizumab did not experience any relapses, suggesting the treatment effectively manages the condition. However, some safety concerns exist. Ravulizumab can increase the risk of serious infections, particularly from the bacteria Neisseria meningitidis, making it crucial for participants to be monitored for signs of infection.

The FDA has already approved ravulizumab for treating NMOSD in adults, providing some confidence in its safety. While the treatment has been tested in adults, this trial aims to gather more information about its safety in children. Participants and their guardians should be aware of these risks and discuss any concerns with the medical team conducting the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ravulizumab is unique because it offers a new approach to treating neuromyelitis optica spectrum disorders (NMOSD). Unlike traditional treatments like rituximab or eculizumab, which target different parts of the immune system, ravulizumab is designed to provide longer-lasting effects by binding to and inhibiting the complement protein C5. This mechanism allows for less frequent dosing, potentially improving convenience and adherence for patients. Researchers are excited about ravulizumab because its extended dosing schedule could lead to better management of NMOSD with fewer infusions, offering a significant improvement in quality of life for those affected by this challenging condition.

What evidence suggests that ravulizumab might be an effective treatment for NMOSD?

Research has shown that ravulizumab, the treatment under study in this trial, greatly reduces the risk of relapse in people with Neuromyelitis Optica Spectrum Disorder (NMOSD). One study showed it lowered the chance of relapse by 98.6%. The treatment works by blocking a part of the immune system that can mistakenly attack the nervous system. Long-term studies indicate that it remains effective over time, providing ongoing protection. This suggests that ravulizumab is a promising option for effectively managing NMOSD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for pediatric patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) who are positive for anti-AQP4 antibodies. They should have an EDSS score ≤ 7 and be stable on current treatments, including eculizumab if applicable. Participants must be vaccinated against meningococcal infections and other specific diseases, and not have used certain immune therapies or participated in conflicting studies recently.

Inclusion Criteria

I have had at least one attack or relapse of my condition in the past year and have not received complement inhibitor treatment.

I am vaccinated against meningococcal infection.

I am positive for anti-AQP4 antibodies and have been diagnosed with NMOSD.

Exclusion Criteria

Participation in another investigational drug or investigational device study (other than Study ECU-NMO-303) within 5 half lives of that investigational product (if known) or 30 days before initiation of the first dose of study drug, whichever is longer

I have not used rituximab in the last 6 months.

I am on, or recently stopped, a biologic medication that affects my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Treatment

Participants receive weight-based dosing of ravulizumab IV

50 weeks

Extension

Participants continue to receive weight-based dosing of ravulizumab IV

up to 104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ravulizumab

Trial Overview The study tests the safety and effectiveness of a medication called Ravulizumab in children with NMOSD. It aims to see how well this drug works in preventing relapses of the disease compared to previous treatments they may have received.

How Is the Trial Designed?

Group I: Ravulizumab Experimental Treatment 1 Intervention

During the Primary Treatment Period, all participants will receive weight-based dosing of ravulizumab IV for a total of 50 weeks of treatment. During the Extension Period, participants will continue to receive weight-based dosing of ravulizumab IV for up to 104 weeks.

Ravulizumab is already approved in United States, European Union for the following indications:

Approved in United States as Ultomiris for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome (aHUS)

Approved in European Union as Ultomiris for:

• Paroxysmal nocturnal haemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Published Research Related to This Trial

In a study involving seven patients with neuromyelitis optica (NMO), treatment with tocilizumab (TCZ) significantly reduced the annualized relapse rate from 2.9 to 0.4 over one year, indicating its efficacy in managing the disease.

TCZ treatment also led to significant improvements in disability scores, neuropathic pain, and fatigue, suggesting that blocking interleukin-6 receptors may be a promising therapeutic strategy for patients with NMO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Araki, M., Matsuoka, T., Miyamoto, K., et al.[2022]

Eculizumab is an effective and safe treatment for Turkish patients with AQP4-IgG+ NMOSD, particularly those with high disease activity, as shown in a study involving 10 patients from the PREVENT and OLE clinical trials.

Patients who discontinued eculizumab treatment experienced early relapses, highlighting the importance of close monitoring for disease reactivation after stopping the medication, especially in those who had previously high disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment. Sen, S., Tuncer, A., Terzi, M., et al.[2023]

A panel of 24 international experts reached a consensus on 25 statements regarding the management of AQP4-IgG-seropositive NMOSD, focusing on the use of three monoclonal antibodies: eculizumab, inebilizumab, and satralizumab.

The consensus included recommendations on treatment initiation, switching therapies, safety considerations, and the use of biomarkers, which can help guide personalized treatment plans for patients with this rare autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International Delphi Consensus on the Management of AQP4-IgG+ NMOSD: Recommendations for Eculizumab, Inebilizumab, and Satralizumab. Paul, F., Marignier, R., Palace, J., et al.[2023]

Monoclonal antibodies significantly reduce the recurrence rate of neuromyelitis optica spectrum disease (NMOSD) in patients, with a hazard ratio of 0.24, indicating a strong protective effect compared to control groups in a meta-analysis of 775 patients.

The safety profile of monoclonal antibodies is comparable to traditional immunosuppressants, with common adverse effects including upper respiratory infections and headaches, but no significant increase in serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of monoclonal antibodies in neuromyelitis optica spectrum disorders: A survival meta-analysis of randomized controlled trials. Xu, X., Xie, L., Wei, L., et al.[2023]

Tocilizumab significantly reduces the annualized relapse rate (ARR) in patients with neuromyelitis optica spectrum disorder (NMOSD), indicating its efficacy in managing this condition, based on a meta-analysis of five clinical trials involving 89 patients.

While 84% of patients experienced adverse effects, most were mild, suggesting that tocilizumab is a relatively safe treatment option for NMOSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis to determine the efficacy and safety of tocilizumab in neuromyelitis optica spectrum disorders. Xie, Q., Zheng, T., Sun, M., et al.[2021]

In the CHAMPION-NMOSD study involving 58 adult patients with anti-aquaporin-4 antibody-positive NMOSD, ravulizumab demonstrated a 98.6% reduction in relapse risk compared to a placebo group from a previous trial, with no patients experiencing relapses during 84 patient-years of treatment.

The safety profile of ravulizumab was consistent with that of eculizumab, with most adverse events being mild to moderate, and no deaths reported, although two patients experienced recoverable meningococcal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Pittock, SJ., Barnett, M., Bennett, JL., et al.[2023]

Eculizumab significantly reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD), with 94.4% of patients remaining relapse-free after 192 weeks of treatment.

The long-term safety profile of eculizumab was consistent with previous findings, showing low rates of treatment-related adverse events and serious infections, and allowing 37% of patients to reduce or stop their background immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD. Wingerchuk, DM., Fujihara, K., Palace, J., et al.[2021]

Eculizumab, a C5 complement inhibitor, shows promise for treating severe cases of neuromyelitis optica spectrum disorders (NMOSD), but carries a risk of meningococcal infection that physicians need to consider.

SA237, an interleukin-6 receptor blocker, may effectively reduce relapse rates and neuropathic pain in NMOSD, while inebelizumab, a B cell depleting agent, is anticipated to be effective based on its similarity to rituximab, despite not being tested in NMOSD yet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational drugs in development to prevent neuromyelitis optica relapses. Paul, F., Murphy, O., Pardo, S., et al.[2019]

Inebilizumab, an anti-CD19 monoclonal antibody, significantly reduced the occurrence of NMOSD attacks in a Phase II/III trial, demonstrating its efficacy in treating this rare autoimmune disease.

The treatment was well tolerated, with fewer participants experiencing worsening disability compared to those receiving a placebo, leading to its FDA approval in 2020 for patients with anti-AQP4 antibody positive NMOSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inebilizumab for treatment of neuromyelitis optica spectrum disorder. J Tullman, M., Zabeti, A., Vuocolo, S., et al.[2022]

Rituximab (RTX) has a relatively low incidence of adverse events (AEs) in patients with neuromyelitis optica spectrum disorder (NMOSD), with 28.57% of patients experiencing any AEs, and most being mild to moderate in severity.

Compared to other immunosuppressants like azathioprine and mycophenolate mofetil, RTX appears to be safer, making it a recommended first-line treatment for NMOSD due to its favorable safety profile and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of rituximab in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. Wang, H., Zhou, J., Li, Y., et al.[2022]

In a phase 3 study involving 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder, eculizumab monotherapy demonstrated a remarkable 96% rate of relapse-free patients after approximately 4 years.

Additionally, 95% of patients receiving eculizumab did not experience worsening of disability, indicating its effectiveness in long-term management of this condition while reducing the need for chronic immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension. Pittock, SJ., Fujihara, K., Palace, J., et al.[2022]

Targeted biologic treatments for neuromyelitis optica spectrum disorder, such as tocilizumab and rituximab, have shown significant efficacy in reducing relapse rates in patients who are aquaporin-4-seropositive, based on recent phase II-III trials.

Most adverse events associated with these treatments were mild to moderate, with common side effects including headaches and infections, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Neuromyelitis Optica Pathogenesis: Results from Randomized Controlled Trials of Biologics. Cacciaguerra, L., Tortorella, P., Rocca, MA., et al.[2023]

Citations

1. ultomirishcp.com ultomirishcp.com/nmosd/efficacy

Efficacy | ULTOMIRIS® (ravulizumab-cwvz) | NMOSD ULTOMIRIS® reduced the risk of relapse by 98.6% (HR=0.014; 95% CI: 0.000‑0.103)2.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11136926/

Network Meta-analysis of Ravulizumab and Alternative ... NMA results suggest ravulizumab, a C5 inhibitor, is likely to be more effective in preventing NMOSD relapse in patients with AQP4-Ab+ NMOSD.

3. neurologylive.com neurologylive.com/view/champion-nmosd-extension-study-supports-long-term-efficacy-ravulizumab-nmosd

CHAMPION-NMOSD Extension Study Supports Long-Term ... Overall, authors noted that these data support the sustained long-term efficacy of ravulizumab-cwvz in adult patients with AQP4 antibody- ...

4. 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- ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Alexion-data-presented-at-the-2025-AAN-Annual-Meeting-highlight-advancements-in-improving-care-for-rare-neurological-diseases.html

Alexion data presented at the 2025 AAN Annual Meeting ... Pittock S, et al. Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum ...

6. ultomirishcp.com ultomirishcp.com/nmosd/safety

Safety | ULTOMIRIS® (ravulizumab-cwvz) | NMOSD ULTOMIRIS, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1)]

7. ultomirishcp.com ultomirishcp.com/nmosd

Neuromyelitis optica spectrum disorder (NMOSD) - Ultomiris Zero relapses were seen in the CHAMPION-NMOSD study1*. ULTOMIRIS® significantly reduced the risk of relapse by 98.6% vs the placebo arm (HR 0.014; ...

8. ultomiris.com ultomiris.com/nmosd

Official NMOSD Patient Site People taking ULTOMIRIS® had ZERO relapses during the clinical trial. ULTOMIRIS is an FDA-approved treatment that reduced the risk of relapse by 98.6% ...

9. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Ravulizumab_ULTOMIRIS_for_NMOSD_Monograph_Addendum_Nov_2024.pdf

Ravulizumab-cwvz (ULTOMIRIS) for the Treatment of ... • Safety data from CHAMPION-NMOSD is summarized in Table 3 ... • Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare CNS inflammatory demyelinating.

10. 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.