A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Basket Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) Encephalitis

Plain English Summary

A Study to Evaluate the Efficacy, Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Satralizumab in Participants With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) Encephalitis is a Phase 3 clinical trial sponsored by Hoffmann-La Roche studying NMDAR Autoimmune Encephalitis, LGI1 Autoimmune Encephalitis. Tests the effectiveness and safety of Satralizumab in treating NMDAR and LGI1 encephalitis. For patients with new onset or incomplete response to treatment for NMDAR or LGI1 encephalitis. Participation involves receiving Satralizumab or placebo through subcutaneous injections every 4 weeks. Alternative treatments include immunosuppressive therapies and other biologic agents. The trial aims to enroll 152 participants.

Official Summary

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

Who Can Participate

Here is what you need to know about eligibility for this trial. Age ≥ 12 years for NMDAR AIE, ≥ 18 years for LGI1 AIE. No history of malignancy or specific infections. Women of childbearing potential must use contraception. Participants must be residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry for extended China enrollment. This trial is studying NMDAR Autoimmune Encephalitis, LGI1 Autoimmune Encephalitis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

Improvement in mRS score and seizure cessation are key outcomes, indicating better quality of life for patients. The specific primary outcome measures are: Part 1: Proportion of Participants in NMDAR AIE Cohort With Modified Rankin Scale (mRS) Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 24 (Baseline up to Week 24); Part 1: Proportion of Participants in LGI1 AIE Cohort With mRS Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 52 (Baseline up to Week 52); Part 2: Percentage of Participants With Adverse Events (AEs) (From Week 52 up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant treatment gap for NMDAR and LGI1 encephalitis, offering a potential new therapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets NMDAR Autoimmune Encephalitis, LGI1 Autoimmune Encephalitis, where improved treatment options are needed.

Investor Insight

Market size is substantial, with a competitive landscape dominated by existing immunosuppressive therapies; approval probability is moderate. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have new onset or incomplete response to treatment for NMDAR or LGI1 encephalitis. Participation involves regular visits and subcutaneous injections every 4 weeks. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 152 participants

Interventions

• DRUG: Satralizumab — In Part 1, study drug will be administered after all other study-related procedures have been performed at a site visit at Weeks 0, 2, 4, and every 4 weeks (Q4W) thereafter. Participants will receive satralizumab according to body weight. Study drug will be administered by subcutaneous (SC) injection in the abdominal or femoral region after all other study-related procedures have been performed at a site visit. In Part 2, participants will be asked to choose from one of the following options: Op
• OTHER: Placebo — Satralizumab placebo prefilled syringe (PFS) is identical in composition to satralizumab PFS, but does not contain the satralizumab active ingredient and will be identical in appearance and packaging to satralizumab. A PFS (assembled with an needle safety device \[NSD\] and extended finger flange) filled with 0.5 milliliters (mL) of solution, corresponding to 60 milligrams (mg) satralizumab, may be used in Part 2 once it becomes available at the study site.

Primary Outcomes

• Part 1: Proportion of Participants in NMDAR AIE Cohort With Modified Rankin Scale (mRS) Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 24 (Baseline up to Week 24)
• Part 1: Proportion of Participants in LGI1 AIE Cohort With mRS Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 52 (Baseline up to Week 52)
• Part 2: Percentage of Participants With Adverse Events (AEs) (From Week 52 up to 2 years)

Secondary Outcomes

• Part 1 (NMDAR AIE Cohort and LGI1 Cohort): Time to mRS Score Improvement ≥ 1 From Baseline Without Use of Rescue Therapy (Baseline up to Week 52)
• Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Time to Rescue Therapy (Baseline up to Week 52)
• Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Proportion of Participants With Sustained Seizure Cessation at Week 24 (Baseline up to Week 24)
• Part 1 (NMDAR AIE Cohort): Change in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score From Baseline at Week 24 (Baseline up to Week 24)
• Part 1 (LGI1 AIE Cohort): Change in CASE Score From Baseline at Week 52 (Baseline up to Week 52)

Full Eligibility Criteria

Inclusion Criteria:

* Reasonable exclusion of tumor or malignancy before baseline visit (randomization)
* Onset of AIE symptoms ≤ 9 months before randomization
* Meet the definition of "New Onset" or "Incomplete Responder" AIE
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab or placebo
* For participants enrolled in the extended China enrollment phase at China's sites: participants who are current residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry

NMDAR AIE Cohort:

* Age ≥ 12 years
* Diagnosis of probable or definite NMDAR encephalitis

LGI1 AIE Cohort

* Age ≥ 18 years
* Diagnosis of LGI1 encephalitis

Exclusion Criteria:

* Any untreated teratoma or thymoma at baseline visit (randomization)
* History of carcinoma or malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before screening
* For participants with NMDAR AIE, history of negative anti-NMDAR antibody in cerebrospinal fluid (CSF) using a cell-based assay within 9 months of symptom onset
* Historically known positivity to an intracellular antigen with high cancer association or glutamate decarboxylase 65 (GAD-65)
* Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1, in the absence of NMDAR and LGI1 antibody positivity
* Confirmed paraneoplastic encephalitis
* Confirmed central or peripheral nervous system demyelinating disease
* Alternative causes of associated symptoms
* History of herpes simplex virus encephalitis in the previous 24 weeks
* Any previous/concurrent treatment with interleukin-6 (IL-6) inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, or bone marrow transplantation
* Any previous treatment with anti-cluster of differentiation 19 antibody (CD19 antibody), complement inhibitors, neonatal Fc receptor antagonists, anti-B-lymphocyte stimulator monoclonal antibody
* Any previous treatment with T-cell depleting therapies, cladribine, or mitoxantrone
* Treatment with oral cyclophosphamide within 1 year prior to baseline
* Treatment with any investigational drug (including bortezomib) within 24 weeks prior to screening
* Concurrent use of more than one immunosuppressive therapy (IST) as background therapy
* Contraindication to all of the following rescue treatments: rituximab, intravenous immunoglobulin (IVIG), high-dose corticosteroids, or intravenous (IV) cyclophosphamide
* Any surgical procedure, except laparoscopic surgery or minor surgeries within 4 weeks prior to baseline, excluding surgery for thymoma or teratoma removal
* Planned surgical procedure during the study
* Evidence of progressive multifocal leukoencephalopathy
* Evidence of serious uncontrolled concomitant diseases
* Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection
* Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection
* Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to baseline visit
* Positive hepatitis B (HBV) and hepatitis C (HCV) test at screening
* Evidence of latent or active tuberculosis (TB)
* History of drug or alcohol abuse within 1 year prior to baseline
* History of diverticulitis or concurrent severe gastrointestinal (GI) disorders that, in the investigator's opinion, may lead to increased risk of complications such as GI perforation
* Receipt of live or live-attenuated vaccine within 6 weeks prior to baseline visit
* History of blood donation (1 unit or more), plasma donation or platelet donation within 90 days prior to screening
* History of severe allergic reaction to a biologic agent
* History of suicide attempt within 3 years prior to screening except if this is clearly associated with and occurs during the acute phase of LGI-1 or NMDAR encephalitis
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes safe participation in and completion of the study
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of study drug

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• UC San Diego, La Jolla, California, United States
• Hoag Memorial Hospital, Newport Beach, California, United States
• UCSF- Multiple Sclerosis Centre, San Francisco, California, United States
• University of Colorado, Aurora, Colorado, United States
• Childrens National Health Center, Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta Center for Advanced Pediatrics, Atlanta, Georgia, United States
• University of Iowa Hospitals & Clinics, Iowa City, Iowa, United States
• University of Maryland Medical Center, Baltimore, Maryland, United States
• Johns Hopkins Hospital, Baltimore, Maryland, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• NMDAR Autoimmune Encephalitis
• LGI1 Autoimmune Encephalitis
• Autoimmune Encephalitis
• Neurological Disorders
• Infectious Diseases
• Immunology
• Neurology
• Autoimmune Diseases
• Encephalitis
• Neurological Conditions

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