Satralizumab for Autoimmune Encephalitis

(Cielo Trial)

Recruiting at 105 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis.

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 satralizumab safe for humans?

Satralizumab has been tested in clinical trials for neuromyelitis optica spectrum disorder (NMOSD) and was generally well tolerated. Common side effects included infections, headaches, joint pain, and reactions at the injection site. ^{1 2 3 4 5}

How is the drug Satralizumab different from other treatments for autoimmune encephalitis?

Satralizumab is unique because it targets the interleukin-6 (IL-6) receptor, which is different from other treatments that may target different pathways or use broader immunosuppressive strategies. This specific targeting can potentially offer a more focused approach to managing autoimmune encephalitis. ^{6 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Complete Relief of Painful Tonic Seizures in Neuromyelitis Optica Spectrum Disorder by Satralizumab Treatment. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Satralizumab: A Review in Neuromyelitis Optica Spectrum Disorder. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Satralizumab: First Approval. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Local experience of IL-6 pathway inhibition with satralizumab for patients with neuromyelitis optica spectrum disorder]. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study. [2022]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

New-onset of Eosinophilic granulomatosis with polyangiitis without eosinophilia and eosinophilic infiltration under benralizumab treatment; a case report. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Severe Eosinophilic Asthma Associated With ANCA-Negative EGPA in a Young Adult Successfully Treated With Benralizumab. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months. [2022]