NMDAR or LGI1 mediated autoimmune Encephalitis MedDRA version: 20.0 Level: PT Classification code 10072378 Term: Encephalitis autoimmune System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Reasonable exclusion of tumor or malignancy before baseline visit (randomization) • Onset of autoimmune encephalitis (AIE) symptoms =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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) • Part 2: To evaluate the long-term safety and tolerability of satralizumab ;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, time to seizure freedom, 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 • 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to mRS score improvement >=1 from baseline without use of rescue therapy 2. Time to rescue therapy 3. Time to seizure freedom (seizure freedom defined as a cessation of seizures for at least 6 consecutive weeks) or cessation of status epilepticus without use of rescue therapy 4. Change in CASE score from baseline at Week 24 5. MOCA total score at Week 24 6. RAVLT score at Week 24 (LGI1 AIE cohort) 7. mRS score at Week 24 (as measured on a 7-point scale; NMDAR AIE cohort) 8. Incidence, seriousness, and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 9. Change from baseline in targeted vital signs, clinical laboratory test results, electrocardiogram (ECG) results, weight, height (<18 years only), and Columbia-Suicide Severity Rating Scale (C-SSRS) ;Timepoint(s) of evaluation of this end point: 1-3. Up to approximately 5 years 4. Baseline (Day -28 to Day 1) to Week 24 5-7. At Week 24 8. Up to approximately 5 years 9. Baseline (Day -28 to Day 1) to approximately 5 years | — |
Countries
Argentina, Austria, Brazil, China, Czech Republic, Denmark, France, Ghana, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed