A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients with NMDAR or LGI1 mediated autoimmune Encephalitis

Phase 1

• Conditions: MDAR or LGI1 mediated autoimmune Encephalitis; MedDRA version: 20.0Level: PTClassification code 10072378Term: Encephalitis autoimmuneSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2021-002395-39-AT
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-01
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 152

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 China's 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 16
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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, 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 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, highdose 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
• A 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
• Laboratory abnormalities at Screening

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • Part 1: To evaluate the efficacy of satralizumab compared with placebo on degree of disability and clinical severity, as measured by a 1 point improvement in the Modified Rankin Scale (mRS)<br>• Part 2: To evaluate the long-term safety and tolerability of satralizumab<br>;Secondary Objective: • Part 1: To evaluate the efficacy of satralizumab compared with placebo<br>based on time to Modified Rankin Scale (mRS score), time to rescue<br>therapy, proportion of participants with sustained seizure cessation,<br>change in Clinical Assessment Scale in Autoimmune Encephalitis (CASE)<br>score, Montreal Overall Cognitive Assessment (MOCA) total score, Rey<br>Auditory Verbal Learning Test (RAVLT) score, and mRS score<br>• Part 1: To evaluate the safety of satralizumab compared with placebo;Primary end point(s): 1. Proportion of participants with mRS score improvement >=1 from baseline and no use of rescue therapy at Week 24;Timepoint(s) of evaluation of this end point: 1. At Week 24