Satralizumab for Autoimmune Encephalitis

(Cielo Trial)

Recruiting at 132 trial locations

Overseen By Reference Study ID Number: WN43174, https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: IL-6 inhibitors, CD19 antibodies

Disqualifiers: Cancer, Demyelinating disease, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 52

Duration: 24 weeks

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of satralizumab, an immunotherapy drug, for individuals with autoimmune encephalitis, where the immune system mistakenly attacks the brain. It focuses on two types: NMDAR and LGI1 encephalitis. The study will evaluate the treatment's effectiveness and safety compared to a placebo, a substance with no active drug. Suitable participants likely experienced symptoms of these specific types of autoimmune encephalitis within the last nine months. The trial aims to discover better treatment options for managing the disease and improving patients' quality of life. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use more than one immunosuppressive therapy at the same time. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research shows that satralizumab is generally safe for people. Its use in other autoimmune diseases suggests relative safety. Previous studies found satralizumab safe and effective for treating autoimmune neurological conditions. Some side effects occurred, but they were usually mild to moderate. Most participants in studies did not experience serious side effects, indicating it is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for encephalitis?

Researchers are excited about satralizumab for autoimmune encephalitis because it offers a novel approach compared to the usual treatments like immunotherapy with steroids, plasma exchange, or intravenous immunoglobulin. Unlike these standard options, satralizumab targets and blocks the interleukin-6 (IL-6) receptor, which plays a role in the inflammatory process associated with this condition. This targeted mechanism could potentially reduce inflammation more effectively and with fewer side effects. Additionally, satralizumab is administered subcutaneously, which might provide a more convenient and less invasive option compared to intravenous treatments. This combination of a targeted approach and easier administration makes satralizumab a promising candidate in the fight against autoimmune encephalitis.

What evidence suggests that satralizumab might be an effective treatment for autoimmune encephalitis?

Research suggests that satralizumab could be helpful for autoimmune encephalitis. In other conditions, satralizumab has effectively reduced inflammation by blocking interleukin-6 (IL-6), a protein involved in the immune system. Patients with similar conditions have experienced symptom improvement. In this trial, participants with NMDAR encephalitis will join either the NMDAR Autoimmune Encephalitis (AIE) Cohort receiving satralizumab or the NMDAR AIE Placebo Cohort. Similarly, participants with LGI1 encephalitis will be in either the LGI1 AIE Cohort receiving satralizumab or the LGI1 AIE Placebo Cohort. While specific results for NMDAR and LGI1 encephalitis are still under study, the mechanism of satralizumab suggests it might help manage these conditions. Early signs indicate it could reduce disease activity and improve quality of life. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for individuals with autoimmune encephalitis, specifically anti-NMDAR or LGI1 encephalitis. Eligible participants must have had symptoms start within the last 9 months and cannot be pregnant or breastfeeding. They should not have a history of certain diseases like tuberculosis, drug abuse, or severe allergies to biologics.

Inclusion Criteria

My autoimmune encephalitis symptoms started less than 9 months ago.

You have recently developed or have not responded well to treatment for an immune-related side effect.

You are currently living in mainland China, Hong Kong, or Taiwan and are of Chinese descent.

Exclusion Criteria

Your test results are not normal when you are screened for the study.

Other reasons for the symptoms you're experiencing.

I do not have any serious uncontrolled diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive satralizumab or placebo to assess efficacy, safety, PK, and PD

24 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Visits at Week 52 and 2 years

Long-term follow-up

Participants are monitored for long-term safety and outcomes

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Satralizumab

Trial Overview The study tests satralizumab's effectiveness and safety in treating autoimmune encephalitis compared to a placebo. It will also look at how the body processes the drug (pharmacokinetics) and its effects on disease activity (pharmacodynamics).

How Is the Trial Designed?

Group I: NMDAR Autoimmune Encephalitis (AIE) Cohort Experimental Treatment 1 Intervention

Adults and adolescents with definite or probable NMDAR encephalitis

Group II: LGI1 AIE Cohort Experimental Treatment 1 Intervention

Adults with LGI1 encephalitis

Group III: NMDAR AIE Placebo Cohort Placebo Group 1 Intervention

Adults and adolescents with definite or probable NMDAR encephalitis

Group IV: LGI1 AIE Placebo Cohort Placebo Group 1 Intervention

Adults with LGI1 encephalitis

Satralizumab is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Enspryng for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive

Approved in European Union as Enspryng for:

• Neuromyelitis optica spectrum disorder (NMOSD)

Approved in Canada as Enspryng for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive

Approved in Japan as Enspryng for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive

Approved in Switzerland as Enspryng for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Chugai Pharmaceutical

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Chugai Pharmaceutical Co.

Collaborator

Trials

4

Recruited

380+

Published Research Related to This Trial

Mepolizumab and benralizumab, both anti-IL-5 therapies, are used to treat refractory eosinophilic granulomatosis with polyangiitis (EGPA), but there is a risk of new-onset EGPA occurring during treatment, as demonstrated in a reported case.

In the case, a patient developed EGPA while on benralizumab, showing symptoms like fever and muscle pain, and was successfully treated with glucocorticoids and cyclophosphamide, highlighting the need for clinicians to monitor for EGPA development in patients receiving anti-IL-5 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New-onset of Eosinophilic granulomatosis with polyangiitis without eosinophilia and eosinophilic infiltration under benralizumab treatment; a case report. Yonezawa, H., Ohmura, SI., Ohkubo, Y., et al.[2023]

In a study of 187 patients with severe eosinophilic asthma, both mepolizumab and benralizumab significantly improved lung function and asthma control over 12 months, with mepolizumab increasing forced expiratory volume (FEV1) from 59% to 74% and benralizumab from 63% to 72%.

Both treatments also led to a significant reduction in oral corticosteroid use and exacerbation rates, showing that they are equally effective long-term options for managing severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months. Kayser, MZ., Drick, N., Milger, K., et al.[2022]

Satralizumab, an anti-IL6 monoclonal antibody, has been approved for treating neuromyelitis optica spectrum disorder (NMOSD) in patients aged 12 and older, showing a safety profile consistent with international clinical trials.

In a small cohort of 16 patients treated under a Compassionate Use Program in Russia, while the short follow-up period limits conclusions on efficacy, satralizumab is considered a valuable treatment option for NMOSD patients who are seropositive for anti-AQP4 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Local experience of IL-6 pathway inhibition with satralizumab for patients with neuromyelitis optica spectrum disorder]. Prakhova, LN., Krasnov, VS., Kasatkin, DS., et al.[2022]

Satralizumab, an interleukin-6 receptor monoclonal antibody, has shown effectiveness in completely resolving painful tonic seizures in a patient with NMOSD after six months of treatment.

The mechanism behind this effect may involve the suppression of microglial activation, which reduces neuronal hyperexcitability, suggesting a potential new use for satralizumab in managing seizure-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Relief of Painful Tonic Seizures in Neuromyelitis Optica Spectrum Disorder by Satralizumab Treatment. Uzawa, A., Mori, M., Iwai, Y., et al.[2022]

In a study of 13 patients with eosinophilic granulomatosis with polyangiitis (EGPA), low-dose mepolizumab (100 mg every 4 weeks) significantly reduced pain and numbness associated with treatment-resistant peripheral neuropathy after 12 months, as measured by visual analogue scale (VAS) scores.

The improvement in symptoms was correlated with decreased levels of eosinophil-derived neurotoxin (EDN) in urine, suggesting a potential mechanism of action, although further placebo-controlled studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose mepolizumab is effective as an add-on therapy for treating long-lasting peripheral neuropathy in patients with eosinophilic granulomatosis with polyangiitis. Nakamura, Y., Fukutomi, Y., Sekiya, K., et al.[2022]

Mepolizumab (MPZ) demonstrated a 100% retention rate in patients with severe eosinophilic granulomatosis with polyangiitis (EGPA), indicating strong adherence and effectiveness as a remission induction therapy compared to intravenous cyclophosphamide (IVCY), which had a completion rate of only 61.5%.

Patients treated with MPZ experienced fewer adverse events (28.6%) compared to those receiving IVCY (53.8%), and the MPZ group showed a significantly greater reduction in corticosteroid doses after 3 months, suggesting MPZ may be a safer and more effective option for managing EGPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study. Ueno, M., Miyagawa, I., Aritomi, T., et al.[2022]

Corticosteroids are recommended for all children with NMDA receptor antibody encephalitis, with pulsed intravenous (IV) administration preferred, and additional treatments like IV immunoglobulin or plasma exchange for severe cases.

For patients who do not respond to initial treatments, second-line therapies such as rituximab are recommended, and maintenance therapy is generally not needed beyond 6 months unless the disease is severe or relapsing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. Nosadini, M., Thomas, T., Eyre, M., et al.[2022]

Satralizumab (Enspryng®) is an effective treatment for neuromyelitis optica spectrum disorder (NMOSD) in AQP4-IgG seropositive patients, significantly reducing relapse risk in phase III trials compared to placebo.

The treatment is well tolerated, with common side effects including infections and headaches, and it is notable for being the first IL-6 receptor blocker approved in the EU for this condition, including for adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Satralizumab: A Review in Neuromyelitis Optica Spectrum Disorder. Fung, S., Shirley, M.[2023]

Satralizumab, an anti-IL-6 receptor monoclonal antibody, received its first global approval in June 2020 for treating neuromyelitis optica spectrum disorder (NMOSD) in patients aged 12 and older who are AQP4-IgG seropositive, based on positive results from two pivotal phase III trials.

The drug has since been approved in multiple countries, including Japan, Switzerland, and the USA, and is currently under review in the EU, highlighting its growing acceptance as a treatment option for NMOSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Satralizumab: First Approval. Heo, YA.[2021]

Benralizumab, a monoclonal antibody targeting the IL-5 receptor, has been successfully used to treat a young female patient with Eosinophilic Granulomatosis with Polyangiitis (EGPA) and a history of severe eosinophilic asthma.

This case highlights a shift in treatment strategies for EGPA, focusing on targeting eosinophils, which play a significant role in the disease's development, rather than relying solely on traditional corticosteroids and immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Severe Eosinophilic Asthma Associated With ANCA-Negative EGPA in a Young Adult Successfully Treated With Benralizumab. Ricciardi, L., Soler, DG., Bennici, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05503264?term=SATRALIZUMAB&rank=9

NCT05503264 | A Study to Evaluate the Efficacy, Safety ... The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis.

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/autoimmune-disorder/autoimmune-encephalitis/a-study-to-evaluate-the-efficacy--safety--pharmacokinet-99237.html

Clinical Trial – NMDAR, LGI1 Autoimmune Encephalitis – Ef... The purpose of this clinical trial is to assess the effectiveness and safety of satralizumab in patients with NMDAR AIE or LGI1 AIE.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11348855/

Innovation and optimization in autoimmune encephalitis trials The primary objective of this study is to evaluate the efficacy, safety, pharmacodynamics (PD), and pharmacokinetics (PK) of satralizumab ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-satralizumab-for-patients-with-autoimmune-encephalitis-nmdar-or-lgi1/

Study on the Effects of Satralizumab for Patients ... The study aims to provide valuable information on the potential benefits and risks of using Satralizumab for treating autoimmune encephalitis, ...

5. duke-research.dukehealth.org duke-research.dukehealth.org/studies/pro00115920

NMDA Satralizumab (Autoimmune Encephalitis) We are doing this study to find out if a drug called satralizumab (the study drug) is a safe and effective option for people with autoimmune encephalitis.

6. nature.com nature.com/articles/s41420-025-02459-z

Immunotherapy for autoimmune encephalitis | Cell Death ... It is a relatively safe, tolerable, and effective treatment for autoimmune neurological diseases. Typically, PE is utilized after steroids and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923011054

Antibody Therapies in Autoimmune Encephalitis In this chapter, we will discuss mAbs targeting B cells (rituximab, ocrelizumab, inebulizumab, daratumumab), IL-6 (tocilizumab, satralizumab), the neonatal Fc ...