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-NL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-07-06
• Last Update Posted: 2 April 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 based on time to Modified Rankin Scale (mRS score), time to rescue therapy, proportion of participants with sustained seizure cessation, change in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score, Montreal Overall Cognitive Assessment (MOCA) total score, Rey Auditory Verbal Learning Test (RAVLT) score, and mRS score<br>• Part 1: To evaluate the safety of satralizumab compared with placebo<br>;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