A Phase 3 Study of Ravulizumab in Adults with NMOSD
Research type
Research Study
Full title
A Phase 3, External Placebo-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)
IRAS ID
275249
Contact name
Daniel Lin
Contact email
Sponsor organisation
Alexion Pharmaceuticals, Inc.
Eudract number
2019-003352-37
ISRCTN Number
ISRCTN00000000
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 7 months, 12 days
Research summary
Summary of Research
This study will investigate the efficacy (effectiveness) and safety of the investigational drug ravulizumab (study drug) given intravenously (IV; in the vein) in Adults with Neuromyelitis Optica Spectrum Disorder (NMOSD). This drug may treat NMOSD by blocking complement activity (the complement system is part of the immune system). Ravulizumab is an experimental drug and therefore unapproved for use in NMOSD globally. A similar drug, eculizumab (SOLIRIS®), has FDA approval (US) for NMOSD.
Developing Ravulizumab to treat NMSOD is based on findings from the clinical development of eculizumab which supports blocking complement activity as a therapy for reducing relapse risk in participants with NMOSD. However, it’s suggested that when compared to eculizumab, Ravulizumab is eliminated from the body slower. This could enable participants to have injections less regularly than with eculizumab, increasing their quality of life while giving comparable benefits.
Ravulizumab (IV) was previously tested in participants with other rare diseases caused by abnormal complement activity. Ravulizumab has been approved under the brand name ULTOMIRIS®™ to treat Paroxysmal Nocturnal Hemoglobinuria (PNH) in the US, Europe, and Japan. This study will be the first to test ravulizumab to treat NMOSD.
This study will recruit approximately 55 subjects globally and have 4 periods; Screening Period, Primary Treatment Period, Long-Term Extension Period, and Safety Follow-up Period. Participants will be screened for up to 6 weeks during the screening. The primary treatment period ends and the Long-Term Extension Period starts when all participants have completed the Week 26 Visit or discontinued early and completed their End of Primary Treatment (EOPT) visit. All participants will continue to receive ravulizumab during the Long-Term Extension Period for up to 2 years, or until ravulizumab is approved and/or available. Following the last dose of the study drug or early discontinuation (ED), participants will be followed for 8 weeks.
Summary of Results
CLINICAL STUDY RESULTS A Study to Learn If Ravulizumab Is Considered Effective and Safe in Adults with Neuromyelitis Optica Spectrum Disorder
THANK YOU!
Alexion would like to thank all of the participants, their families, and caregivers who took part in this clinical study. Taking part in studies may contribute directly to the discovery of new treatments for people with neuromyelitis optica spectrum disorder.STUDY IDENTIFICATION INFORMATIONTREATMENTS STUDIED: Ravulizumab, also known as ALXN1210 (trade name: Ultomiris®) STUDY TITLE: A Phase 3, External Placebo-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) STUDY NUMBERS: United States, NCT04201262 | European Union, 2019-003352-37 | Protocol, ALXN1210 NMO 307
What was the purpose of this study?
In this study, a drug called ravulizumab was tested. The researchers wanted to know how effective, safe, and tolerable ravulizumab was in the treatment of adults with neuromyelitis optica spectrum disorder (also known as NMOSD). Researchers measured how long participants went without a relapse (periods of new or worsening NMOSD symptoms) while taking ravulizumab to determine whether the drug worked.
Clinical trials aim to answer questions about specific diseases, or treatment procedures, and involve participants with medical conditions or healthy volunteers. Clinical studies to develop new treatments happen in four stages, from Phase 1 to Phase 4, each investigating specific questions about the treatment.
This was a Phase 3 study. Phase 3 studies look at the overall risks and benefits of a treatment compared to a control group. In this study, researchers compared participants who took ravulizumab to participants who took a placebo in an earlier study of the same disease. Placebo is a product that looks like the treatment being tested, but contains no real medicine.What is neuromyelitis optica spectrum disorder?
NMOSD is an ultra-rare condition that causes swelling around a person’s optic nerves and spinal cord. It is an autoimmune disease, which means that the body’s natural defenses mistakenly attack healthy tissue. NMOSD is a life- long condition.What are the symptoms of neuromyelitis optica spectrum disorder?
Symptoms may vary, but often include eye pain or blindness, weakness or loss of functionality in arms or legs, and loss of bladder or bowel control. Patients with NMOSD are at risk of relapses, which can further damage the optic nerves and spinal cord, and lead to worsening of symptoms. Some damage may be irreversible, resulting in permanent symptoms and disability. It is more common in biological females than males and among people of African or Asian ancestry. It is usually diagnosed in young adults, but can occur at any age.What treatments are available for neuromyelitis optica spectrum disorder?
Treating NMOSD focuses on preventing relapses and minimizing the damage of this disease.
Several treatments are currently available. All treatments aim to decrease immune system activity. Examples include corticosteroids (like methylprednisolone or prednisone) and immunosuppressive therapies (like rituximab and mycophenolate). However, none of these are approved to treat NMOSD.
Ravulizumab (Ultomiris®) and eculizumab (Soliris®) are two drugs approved to treat NMOSD.
Both drugs work by blocking a part of the immune system called the “complement system”.
Blocking the complement system helps prevent further damage to the optic nerves and spinal cord. Satralizumab (Enspryng®) and inebilizumab (Uplizna®) are two other drugs approved to treat NMOSD. These also work by blocking other parts of the immune system, but do not directly affect the complement system.
All four of these drugs are given as intravenous (IV; administered through a vein) infusions, which can take anywhere from 30 minutes to several hours. Patients usually receive these infusions at a hospital or clinic. Eculizumab requires infusions every two weeks, but ravulizumab remains active in most people’s bodies about four times longer than eculizumab, so patients usually take ravulizumab once every two months.
Ravulizumab is also approved to treat several other rare diseases. This study was intended to evaluate whether ravulizumab is effective for the treatment of NMOSD.What treatments were researched in this study?
In this study, all participants received ravulizumab, given intravenously. Throughout the study, all participants were given “open-label” ravulizumab, which means that the participants, participants’ caregivers, and the study doctors knew which dose/treatment was received.
Participants started with a one-time “loading dose” of ravulizumab on their first day. All remaining doses were “maintenance doses” that participants took every 2 months. All doses were based on the bodyweight of the individual participant.Who could take part in this study?
Male or female adults (18 years old or older)Confirmed diagnosis of NMOSD and at least 1 attack within 12 months of starting the study
Score of 7 or less on the Expanded Disability Status Scale (EDSS) examination, which generally means requiring a wheelchair for mobility, with lower scores associated with more mobility
People could not participate if they had ever had an N. meningitidis infection (a potentially serious bacterial infection also called meningococcal disease). Doctors also checked for other medical conditions that could risk a participant’s health or interfere with study results.
People could not participate if they had ever taken a different drug that works the same way as ravulizumab. They also could not have taken certain immune system suppressors within 3 months of starting the study.
Participants consented to be in the study.How many participants took part in this study?
52 adult females + 6 adult males = 58 adult participantsParticipants were between 18 and 74 years of age at the start of the first infusion.
The study started in December 2019 and ended in November 2024.WHERE WAS THIS STUDY DONE?
The study took place in 36 study centers in 11 countries:
Australia, Canada, Denmark, Germany, Italy, Japan, Poland, South Korea, Spain, United Kingdom, United States.WHAT WERE THE RESULTS OF THIS STUDY?
The researchers wanted to see how safe and effective ravulizumab was in the treatment of participants with NMOSD after at least 50 weeks.
During the study, researchers looked for any side effects on the participants. Side effects could include severe reactions to the drug. If any serious health effect was found, the researchers determined if the participants could continue receiving the treatment.How long did participants remain free from NMOSD relapse while taking ravulizumab?
Ravulizumab – 100% of participants NMOSD relapse free after about 2 years.
Placebo – 52% of participants NMOSD relapse free after about 2 years.All participants taking ravulizumab remained relapse free for their entire time in the study, from 0.2 to 4.7 years. All but two participants remained in the study for more than 2 years.
With NMOSD, remission means the periods of time when the disease is not actively damaging the body. Remission can last months or years. The possibility for future “relapse” remains, and patients may still have symptoms from previous relapse.
None of the 58 participants (0%) who took ravulizumab had a relapse of NMOSD. Participants who were in the study the longest had their NMOSD remain in remission for 3.3 years or longer. In comparison, 20 out of 47 participants (42.6%) who took placebo in a different study had a relapse.What were the safety findings in this study?
A side effect is any symptom a participant has during the study which may or may not be related to the study treatment. Related side effects are unwanted medical events that happen during the study, and are considered to be related to the study treatment. Side effects are classified as either “mild”, “moderate”, or “severe” in intensity.
A serious side effect is thought to be an important medical event (e.g., requires a person to be admitted to the hospital, is life-threatening, causes disability, or causes death).
Side effects can vary from person to person. Researchers keep a record of all the side effects participants have when new treatments are studied. This helps researchers to determine which side effects occur as a result of the study treatment, and which occur by chance or because of the participant’s underlying disease.What serious side effects did participants have in this study?
Overall, 16 out of 58 participants (27.6%) had serious side effects during the study, the majority of which were thought by the study doctors to be not related to ravulizumab.
A total of 2 out of 58 participants (3.4%) experienced related serious side effects of meningococcal disease, an illness caused by infection with the bacteria Neisseria meningitidis.
These infections can be life-threatening and may result in septicemia (blood poisoning), meningitis (inflammation around the brain and spinal cord), and pneumonia (infection of the lungs), and may be life-threatening if not promptly diagnosed and treated. Both participants in this study were promptly treated and made a full recovery.What side effects did participants have in this study?
Overall, 55 out of 58 participants (94.8%) had side effects during the study, the majority of which were thought by the study doctors to be unrelated to ravulizumab. A total of 27 out of 58 participants (46.6%) had a side effect that was thought by the study doctors to be related to ravulizumab.
The most common related side effects, which happened in 3 or more participants in the study, are shown below:Most Common Related Side Effects Ravulizumab (58 participants) Related side effects in 3 or more participants in the study 27 (46.6%) Most Common Related Side Effects Cystitis (bladder infection that can cause pain during urination) 3 (5.2%) Infusion-related reaction (any symptom that occurs during or shortly after infusion) 3 (5.2%) Headache 3 (5.2%) Nasopharyngitis (inflammation of the nose and throat) 3 (5.2%)
Were there any other important safety findings in this study?
One out of 58 participants (1.7%) stopped taking ravulizumab because of side effects. These side effects included encephalitis meningococcal, stenotrophomonas infection, and bronchitis, which occurred simultaneously.OUTCOME OF THE STUDY
How has this study helped participants and researchers?
The information collected in this study showed that ravulizumab is effective, safe, and tolerable in adults with NMOSD. The majority of side effects were thought by the study doctors to be unrelated to ravulizumab.Before a treatment can be approved for patients to use, researchers look at the results of many studies to decide which treatments work best and are safe. If you have any questions about ravulizumab for the treatment of NMOSD, please talk to your doctor. You should not change your treatment based on the results of this study, without talking to a doctor first.
Useful clinical study websites
This document provides a summary of the main results of the study. It includes information about the side effects that happened to participants in the study and the results of the questions the researchers wanted to answer. This summary was reviewed for readability by a patient advocacy group.Additional study results are available at the following clinical study register(s):
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7Ca2f73965185c4a53ed4908dde7091258%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638920748381684564%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=YfgEtrBRBZA%2FyHlbSDn8xw1h7y1pGN05lLLX3iE9MZM%3D&reserved=0
Use the study number NCT04201262 to search for more information on this website.
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7Ca2f73965185c4a53ed4908dde7091258%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638920748381701159%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=pVeHle2I68cp9kvXi8nxet4MJYhaMvviXQWEqsjv8bE%3D&reserved=0
Use the study number 2019-003352-37 to search for more information on this website.Further studies
There are currently two other studies of ravulizumab for people with NMOSD.
• In Canada, France, Germany, Italy, Japan, South Korea, Spain, and United States:
ALXN‑NMO‑317, efficacy and safety of ravulizumab in children with NMOSD; details available at https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT05346354%2FNBTI%2FKq_-AQ%2FAQ%2F9cc7ef54-1149-4af0-81c0-a7c2734ac6df%2F2%2F8EFnOq-clE&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7Ca2f73965185c4a53ed4908dde7091258%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638920748381717339%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=e8T6bKFXmLR5E%2FaAvvYNeFeNJGBS9eK28viCQSmCLiI%3D&reserved=0 and https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Feuclinicaltrials.eu%252Fctis-public%252Fview%252F2023-508534-33-00%2FNBTI%2FKq_-AQ%2FAQ%2F9cc7ef54-1149-4af0-81c0-a7c2734ac6df%2F3%2F6NDh8u2p8Y&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7Ca2f73965185c4a53ed4908dde7091258%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638920748381733204%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=lgZvBR94JVS2W1huYhfhGtiomxHF%2FG9Xmzl%2BeSfbXxQ%3D&reserved=0
• In Argentina, Canada, China, Germany, Italy, Japan, South Korea, and United States: registry of patients with AQP4+ NMOSD, who have been treated with an Alexion C5 inhibitor; details available at https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT05966467%2FNBTI%2FKq_-AQ%2FAQ%2F9cc7ef54-1149-4af0-81c0-a7c2734ac6df%2F4%2FKpK5e59PXK&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7Ca2f73965185c4a53ed4908dde7091258%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638920748381748993%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=8SDF4yCgYfUWnSi6N1y3leeikknzuiAfbFjt47BTuRk%3D&reserved=021 August 2025 | This summary includes known facts as of the time the document was finalized.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
20/EE/0050
Date of REC Opinion
30 Apr 2020
REC opinion
Further Information Favourable Opinion