BRAIN Inflammation and encephalitis
Conditions
Interventions
During Part 1, participants will be randomly assigned in a 1:1 ratio to receive
placebo or 60 mg, 120 mg, or 180 mg depending of weight satralizumab in each of
the NMDAR AIE and LGI1 AIE cohorts.
Sponsors
Roche Nederland B.V.
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: Zie paraaf 5.1. en 5.2 in het protocol V2 Inclusion Criteria for All Participants * Capable of giving signed informed consent as described in Appendix 1 * Reasonable exclusion of tumor or malignancy before baseline visit (randomization) * Onset of AIE symptoms, 2, measured at baseline - Has received their first acute first-line therapy within 6 weeks prior to randomization (baseline visit) - Has not received prior treatment with rituximab or any other ISTs (e.g., cyclophosphamide, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, azathioprine) or tocilizumab for AIE - Incomplete Responder: defined as a participant with NMDAR or LGI1 AIE who satisfies the following criteria: o Has a stable (for at least 24 hours) mRS score = or > 2, measured at baseline o Has received their first acute first-line therapy more than 6 weeks prior to randomization (baseline visit). o Has received immunotherapy beyond their first acute first-line therapy course. * For women of childbearing potential: agreement to remain abstinent or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab or placebo Additional Inclusion Criteria for the NMDAR AIE Cohort In addition to the criteria outlined in Section 5.1.1, participants are eligible to be included in the NMDAR AIE cohort only if all of the following criteria apply: * Age, > 12 years at the time of signing Informed Consent Form * Signed Assent Form * Diagnosis of probable or definite NMDAR encephalitis Additional Inclusion Criteria for the LGI1 AIE Cohort In addition to the criteria outlined in Section 5.1.1, participants are eligible to be included in the LGI1 AIE cohort only if all of the following criteria apply: * Age, > 18 years at the time of signing Informed Consent Form * Diagnosis of LGI1 encephalitis
Exclusion criteria
Exclusion criteria: * Any untreated teratoma or thymoma at baseline visit (randomization). Teratoma or thymoma detected prior to or during the screening period is allowed if deemed cured after treatment (usually surgical removal) by 1 week prior to baseline * History of carcinoma or malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for = and > 5 years before screening (except basal cell and squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri that have been completely excised and cured) * For patients with NMDAR AIE, history of negative anti-NMDAR antibody in CSF using a cell based assay within 9 months of symptom onset * Historically known positivity to an intracellular antigen with high cancer association (e.g., anti-Hu, anti-Ma2, anti-CRMP5, anti-Yo, anti-amphiphysin, AMPA, mGluR5, and GABAB) or GAD-65 * Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1 (e.g., caspr2, IgLON5, DPPX, GABAA, and neurexin-3a) * Confirmed paraneoplastic encephalitis * Confirmed central or peripheral nervous system demyelinating disease (e.g., multiple sclerosis, chronic inflammatory demyelinating polyneuropathy) * Alternative causes of associated symptoms, including CNS infections, septic encephalopathy, metabolic encephalopathy, epileptic disorders, mitochondrial disease, Klein-Levin syndrome, Creutzfeldt-Jakob disease, rheumatologic disorders, Reyes syndrome, or inborn errors of metabolism * 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 (e.g., belimumab) * 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 (or within 5 half-lives of the investigational drug; whichever is longer) * Concurrent use of more than one IST (e.g.. azathioprine, mycophenolate mofetil, or IV cyclophosphamide) as background therapy The combination of an OCS with another permitted IST drug is allowed. * Contraindication to all of the following rescue treatments: rituximab, IVIG, high-dose corticosteroids, or IV cyclophosphamide * Any surgical procedure, except laparoscopic surgery or minor surgeries (defined as procedures that require only local anesthesia or conscious sedation, i.e., do not require general, neuraxial or regional anesthesia, and are done on an ambulatory/outpatient basis; e.g. toenail surgery, mole surgical excision, wisdom tooth extraction), within 4 weeks prior to baseline, excluding surgery for thymoma or teratoma removal * Planned surgical procedure (except minor surgeries) during the study * Evidence of progressive multifocal leukoencephalopathy * Evidence of serious uncontrolled concomitant diseases that may preclude patient participation, such as other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of satralizumab compared with placebo on degree of disability and clinical severity: • Proportion of participants with mRS score improvement = or > 1 from baseline and no use of rescue therapy at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| A. To evaluate the efficacy of satralizumab compared with placebo: • Time to mRS score improvement = or > 1 from baseline without use of rescue therapy • Time to rescue therapy • 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 • Change in CASE score from baseline at Week 24 • MOCA total score at Week 24 • RAVLT score at Week 24 (LGI1 AIE cohort) • mRS score at Week 24 (as measured on a 7-point scale; NMDAR AIE cohort) B. To evaluate the safety of satralizumab compared with placebo: • Incidence, seriousness, and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 • Change from baseline in targeted vital signs, clinical laboratory test results, ECG results, weight, height ( | — |
Countries
Netherlands
Outcome results
None listed