El propósito de este estudio es evaluar la eficacia, seguridad, farmacocinética (FK) y farmacodinámica (FD) de satralizumab en participantes con encefalitis por NMDAR y LGI1.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

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: Option 1: continue on randomized, double-blind study drug; Option 2: start open-label satralizumab based on body weight; Option 3: stop study treatment and continue follow-up assessments.

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.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Satralizumab

Placebo

Ubicaciones

Hospital Ramos Mejía

Hospital Britanico

Sanatorio del Sur S.A.

Patrocinadores

Contactos

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

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