A Study to Evaluate the Efficacy, Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Satralizumab in Participants With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) Encephalitis

Purpose

The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis.

Conditions

  • NMDAR Autoimmune Encephalitis
  • LGI1 Autoimmune Encephalitis

Eligibility

Eligible Ages
Over 12 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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

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 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NMDAR Autoimmune Encephalitis (AIE) Cohort 		Adults and adolescents with definite or probable NMDAR encephalitis
  • 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.
Experimental
LGI1 AIE Cohort 		Adults with LGI1 encephalitis
  • 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.
Placebo Comparator
NMDAR AIE Placebo Cohort 		Adults and adolescents with definite or probable NMDAR encephalitis
  • 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.
Placebo Comparator
LGI1 AIE Placebo Cohort 		Adults with LGI1 encephalitis
  • 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.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233

UC San Diego
La Jolla, California 92037

Hoag Memorial Hospital
Newport Beach, California 92658

UCSF- Multiple Sclerosis Centre
San Francisco, California 94158

University of Colorado
Aurora, Colorado 80045

Childrens National Health Center
Washington D.C., District of Columbia 20010

Children's Healthcare of Atlanta Center for Advanced Pediatrics
Atlanta, Georgia 30329

University of Iowa Hospitals & Clinics
Iowa City, Iowa 52242

University of Maryland Medical Center
Baltimore, Maryland 21201

Johns Hopkins Hospital
Baltimore, Maryland 21205

Brigham and Women's Hospital Department of Neurology
Boston, Massachusetts 02115

Mayo Clinic - Rochester
Rochester, Minnesota 55905

NYU-Langone Medical Center
New York, New York 10016

Duke University Medical Center
Durham, North Carolina 27710

University Hospitals of Cleveland
Cleveland, Ohio 44106

Cleveland Clinic Foundation
Cleveland, Ohio 44915

Univ of Pennsylvania Med Ctr
Philadelphia, Pennsylvania 19104

University of Texas at Houston
Houston, Texas 77030

Medical College of Wisconsin
Milwaukee, Wisconsin 53226

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: WN43174, https://forpatients.roche.com/
888-662-6728 (U.S.)
global-roche-genentech-trials@gene.com