A 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 (Cielo)

This is an interventional treatment trial for NMDAR Autoimmune Encephalitis Read More

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