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 (Cielo)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Basket Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) Encephalitis

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

Study Overview

• Status: Recruiting
• Conditions: NMDAR Autoimmune Encephalitis; LGI1 Autoimmune Encephalitis
• Intervention / Treatment: Drug: Satralizumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WN43174, https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S.); Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Global Medical Information:; Email: global.medical_information@roche.com

Study Locations

• Argentina
  • CABA, Argentina, C1221ADC
    • Active, not recruiting
    • Hospital Ramos Mejía
  • Ciudad Autonoma Bs As, Argentina, C1280AEB
    • Recruiting
    • Hospital Britanico
  • San Miguel de Tucumán, Argentina, T4000IDK
    • Recruiting
    • Sanatorio del Sur S.A.
• Austria
  • Linz, Austria, 4020
    • Withdrawn
    • Kepler Universitätsklinikum GmbH - Neuromed Campus
  • Vienna, Austria, 1090
    • Withdrawn
    • Medizinische Universität Wien
• Brazil
  • Ceará
    • Fortaleza, Ceará, Brazil, 60175-295
      • Recruiting
      • Hospital Geral de Fortaleza
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055-450
      • Recruiting
      • CEDOES - Diagnóstico e Pesquisa
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Recruiting
      • Instituto de Neurologia de Curitiba
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05652-000
      • Recruiting
      • Hospital Israelita Albert Einstein
    • São Paulo, São Paulo, Brazil, 01228-200
      • Recruiting
      • Centro de Pesquisas Clinicas
• China
  • Beijing, China, 100730
    • Recruiting
    • Beijing Tongren Hospital
  • Beijing, China, 100045
    • Recruiting
    • Beijing Children's Hospital, Capital Medical University
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital,Capital Medical University
  • Changchun, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Changsha, China, 410011
    • Recruiting
    • The Second Xiangya Hospital Of Central South University
  • Chengdu, China, 610047
    • Recruiting
    • West China Hospital - Sichuan University
  • Fuzhou, China, 350001
    • Recruiting
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510180
    • Recruiting
    • Guangzhou First Municipal People's Hospital
  • Jining, China, 272029
    • Recruiting
    • Affiliated Hospital of Jining Medical University
  • Shanghai, China, 200040
    • Recruiting
    • Huashan Hospital, Fudan University
  • Taiyuan, China, 030001
    • Recruiting
    • The First Hospital of Shanxi Medical University
  • Wenzhou, China, 325035
    • Completed
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430030
    • Recruiting
    • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Withdrawn
    • Fakultni nemocnice Hradec Kralove
  • Prague, Czechia, 150 06
    • Recruiting
    • Fakultni nemocnice v Motole
• Denmark
  • Odense C, Denmark, 5000
    • Recruiting
    • Odense Universitetshospital, Neurologisk Afdeling N
• France
  • Bron, France, 69677
    • Completed
    • Hopital neurologique Pierre Wertheimer - CHU Lyon
  • Paris, France, 75651
    • Recruiting
    • Hopital Pitié Salpétrière - CHU
  • Saint-Etienne, France, 42055
    • Withdrawn
    • CHU Saint Etienne - Hôpital Nord
  • Tours, France, 37000
    • Recruiting
    • CHRU - Hôpital Bretonneau
• Ghana
  • Kumasi, Ghana
    • Recruiting
    • Komfo Anokye Teaching Hospital
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah University Hospital Ein Kerem
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Recruiting
      • A. O. U. Federico II
    • Naples, Campania, Italy, 80138
      • Recruiting
      • AOU Seconda Università degli Studi
  • Lazio
    • Rome, Lazio, Italy, 00165
      • Withdrawn
      • Ospedale Pediatrico Bambino Gesù
  • Liguria
    • Genoa, Liguria, Italy, 16132
      • Recruiting
      • Irccs A.O.U.San Martino Ist
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • Recruiting
      • IRCCS Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Pavia, Lombardy, Italy, 27100
      • Recruiting
      • Fondazione Istituto Neurologico Mondino IRCCS
  • Sicily
    • Palermo, Sicily, Italy, 90129
      • Recruiting
      • AOU Policlinico Giaccone
• Japan
  • Aichi, Japan, 470-1192
    • Recruiting
    • Fujita Health University Hospital
  • Chiba, Japan, 260-8677
    • Active, not recruiting
    • Chiba University Hospital
  • Fukuoka, Japan, 812-8582
    • Completed
    • Kyushu University Hospital
  • Fukuoka, Japan, 814-0180
    • Recruiting
    • Fukuoka University Hospital
  • Gifu, Japan, 501-1194
    • Recruiting
    • Gifu University Hospital
  • Hokkaido, Japan, 060-8648
    • Active, not recruiting
    • Hokkaido University Hospital
  • Hyogoken, Japan, 6500047
    • Recruiting
    • Hyogo Prefectural Kobe Children's Hospital
  • Hyōgo, Japan, 650-0017
    • Recruiting
    • Kobe University Hospital
  • Kagoshima, Japan, 890-8760
    • Recruiting
    • Kagoshima City Hospital
  • Kanagawa, Japan, 259-1193
    • Recruiting
    • Tokai University Hospital
  • Kanagawa, Japan, 252-0375
    • Active, not recruiting
    • Kitasato University Hospital
  • Kanagawa, Japan, 216-8511
    • Completed
    • St.Marianna University School of Medicine hospital
  • Miyagi, Japan, 980-8574
    • Recruiting
    • Tohoku University Hospital
  • Osaka, Japan, 565-0871
    • Recruiting
    • The University of Osaka Hospital
  • Osaka, Japan, 590-0197
    • Recruiting
    • Kindai University Hospital
  • Saitama, Japan, 362-8588
    • Recruiting
    • Ageo Central General Hospital
  • Tokyo, Japan, 173-8610
    • Recruiting
    • Nihon University Itabashi Hospital
  • Tokyo, Japan, 113-8431
    • Recruiting
    • Juntendo University Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus MC
• Poland
  • Grudzi?dz, Poland, 86-300
    • Withdrawn
    • Regionalny Szpital Specjalistyczny im. W. Bieganskiego
  • Krakow, Poland, 30-688
    • Completed
    • Szpital Uniwersytecki w Krakowie
  • Warsaw, Poland, 02-957
    • Recruiting
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
  • Zabrze, Poland, 41-800
    • Recruiting
    • SPSK nr 1
• Singapore
  • Singapore, Singapore, 308433
    • Recruiting
    • National Neuroscience Institute
  • Singapore, Singapore, 117599
    • Recruiting
    • National University Hospital (NUH)
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Regional Universitario de Malaga ? Hospital General
  • Pontevedra
    • Vigo, Pontevedra, Spain, DUMMY_VALUE
      • Recruiting
      • Hospital Alvaro Cunqueiro
• Taiwan
  • Kaohsiung City, Taiwan, 00833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • North Dist., Taiwan, 40402
    • Withdrawn
    • China Medical University Hospital
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital - Linkou
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • UC San Diego
    • Newport Beach, California, United States, 92658
      • Recruiting
      • Hoag Memorial Hospital
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF- Multiple Sclerosis Centre
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Childrens National Health Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Children's Healthcare of Atlanta Center for Advanced Pediatrics
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Withdrawn
      • University of Iowa Hospitals & Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital Department of Neurology
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU-Langone Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Of Cleveland
    • Cleveland, Ohio, United States, 44915
      • Recruiting
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Withdrawn
      • Univ of Pennsylvania Med Ctr
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas at Houston
  • Washington
    • Seattle, Washington, United States, 98122
      • Withdrawn
      • Swedish Neuroscience Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Proportion of Participants in NMDAR AIE Cohort With Modified Rankin Scale (mRS) Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 24	Baseline up to Week 24
Part 1: Proportion of Participants in LGI1 AIE Cohort With mRS Score Improvement ≥ 1 From Baseline and no Use of Rescue Therapy at Week 52	Baseline up to Week 52
Part 2: Percentage of Participants With Adverse Events (AEs)	From Week 52 up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (NMDAR AIE Cohort and LGI1 Cohort): Time to mRS Score Improvement ≥ 1 From Baseline Without Use of Rescue Therapy		Baseline up to Week 52
Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Time to Rescue Therapy		Baseline up to Week 52
Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Proportion of Participants With Sustained Seizure Cessation at Week 24	Sustained seizure cessation is defined as 4 consecutive weeks of no seizures maintained until Week 24 and no use of rescue therapy.	Baseline up to Week 24
Part 1 (NMDAR AIE Cohort): Change in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score From Baseline at Week 24		Baseline up to Week 24
Part 1 (LGI1 AIE Cohort): Change in CASE Score From Baseline at Week 52		Baseline up to Week 52
Part 1 (NMDAR AIE Cohort): Montreal Overall Cognitive Assessment (MOCA) Total Score at Week 24		Baseline up to Week 24
Part 1 (LGI1 AIE Cohort): MOCA Total Score at Week 52		Baseline up to Week 52
Part 1 (LGI1 AIE Cohort): Rey Auditory Verbal Learning Test (RAVLT) Score at Week 52		Baseline up to Week 52
Part 1 (NMDAR AIE Cohort): mRS Score at Week 24 (as Measured on a 7-point Scale)		Baseline up to Week 24
Part 1: Percentage of Participants With AEs	Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5.0)	Baseline, Week 52, 2 Years
Parts 1 and 2: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk.	Baseline up to 2 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2022
• Primary Completion (Estimated): December 16, 2026
• Study Completion (Estimated): December 14, 2029

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Epilepsy; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Epilepsies, Partial; Autoimmune Diseases of the Nervous System; Hashimoto Disease; satralizumab
• Other Study ID Numbers: WN43174; 2021-002395-39 (EudraCT Number); 2023-504226-18-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No