Overview
The purpose of this study is to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab in participants with anti-N-methyl-D-aspartic acid receptor (NMDAR) and anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.
Eligibility
Inclusion Criteria:
- Reasonable exclusion of tumor or malignancy before baseline visit (randomization)
- Onset of autoimmune encephalitis (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 National Medical Products Administration (NMPA)-recognized sites: participants who are current residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry
N-methyl-D-aspartic acid receptor (NMDAR) AIE Cohort
- Age >=12 years
- Diagnosis of probable or definite NMDAR encephalitis
Leucine-rich glioma-inactivated 1 (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 patients 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 GAD-65
- Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1
- 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 IL-6 inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, or bone marrow transplantation
- Any previous treatment with anti-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 IST as background therapy
- Contraindication to all of the following rescue treatments: rituximab, 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 that may preclude patient participation
- Congenital or acquired immunodeficiency, including 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
- Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
- 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
- Laboratory abnormalities at Screening