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

NCT05503264 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: WN431742021-002395-392023-504226-18-00
• Study Type: interventional
• Target: 122
• Locations: 17 countries
• Sites: 77

Brief Summary

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

Outcome Measures

Primary Outcomes (3)

• 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 4 years

Secondary Outcomes (11)

• 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

  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

Study Arms (4)

NMDAR Autoimmune Encephalitis (AIE) Cohort

EXPERIMENTAL

Adults and adolescents with definite or probable NMDAR encephalitis will receive satralizumab as per the schedule specified in the protocol. As of Protocol Version 6, participants in Part 1 will transition to Part 2 at the time of primary analysis or at Week 52, whichever occurs first.

Drug: Satralizumab

LGI1 AIE Cohort

EXPERIMENTAL

Adults with LGI1 encephalitis as per the schedule specified in the protocol.

Drug: Satralizumab

NMDAR AIE Placebo Cohort

PLACEBO COMPARATOR

Adults and adolescents with definite or probable NMDAR encephalitis will receive satralizumab placebo as per the schedule specified in the protocol. As of Protocol Version 6, participants in Part 1 will transition to Part 2 at the time of primary analysis or at Week 52, whichever occurs first.

Other: Placebo

LGI1 AIE Placebo Cohort

PLACEBO COMPARATOR

Adults with LGI1 encephalitis will receive satralizumab placebo as per the schedule specified in the protocol.

Other: Placebo

Interventions

Satralizumab DRUG

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, administered as 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. As of Protocol Version 6, participants in the NMDAR cohort who chose Option 1 will transition to either Option 2 or Option 3 at the time of the primary analysis.

Also known as: Enspryng; RO5333787

LGI1 AIE Cohort; NMDAR Autoimmune Encephalitis (AIE) Cohort

Placebo OTHER

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.

LGI1 AIE Placebo Cohort; NMDAR AIE Placebo Cohort

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 nervous system (CNS) or peripheral nervous system (PNS) 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (77)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

UC San Diego

La Jolla, California, 92037, United States

Location

Hoag Memorial Hospital

Newport Beach, California, 92658, United States

Location

UCSF- Multiple Sclerosis Centre

San Francisco, California, 94158, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Childrens National Health Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta Center for Advanced Pediatrics

Atlanta, Georgia, 30329, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Brigham and Women's Hospital Department of Neurology

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

NYU-Langone Medical Center

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44915, United States

Location

University of Texas at Houston

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Ramos Mejía

CABA, C1221ADC, Argentina

Location

Hospital Britanico

Ciudad Autonoma Bs As, C1280AEB, Argentina

Location

Sanatorio del Sur S.A.

San Miguel de Tucumán, T4000IDK, Argentina

Location

Hospital Geral de Fortaleza

Fortaleza, Ceará, 60175-295, Brazil

Location

CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, 29055-450, Brazil

Location

Instituto de Neurologia de Curitiba

Curitiba, Paraná, 81210-310, Brazil

Location

Centro de Pesquisas Clinicas

São Paulo, São Paulo, 01228-200, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05652-000, Brazil

Location

Beijing Children's Hospital, Capital Medical University

Beijing, 100045, China

Location

Beijing Tongren Hospital

Beijing, 100730, China

Location

Beijing Tiantan Hospital,Capital Medical University

Beijing, China

Location

West China Hospital - Sichuan University

Chengdu, 610047, China

Location

Fujian Medical University Union Hospital

Fuzhou, 350001, China

Location

Affiliated Hospital of Jining Medical University

Jining, 272029, China

Location

Huashan Hospital, Fudan University

Shanghai, 200040, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325035, China

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Odense Universitetshospital, Neurologisk Afdeling N

Odense C, 5000, Denmark

Location

Hopital neurologique Pierre Wertheimer - CHU Lyon

Bron, 69677, France

Location

Hopital Pitié Salpétrière - CHU

Paris, 75651, France

Location

CHRU - Hôpital Bretonneau

Tours, 37000, France

Location

Komfo Anokye Teaching Hospital

Kumasi, Ghana

Location

Hadassah University Hospital Ein Kerem

Jerusalem, 9112001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

A. O. U. Federico II

Naples, Campania, 80131, Italy

Location

Irccs A.O.U.San Martino Ist

Genoa, Liguria, 16132, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Lombardy, 20133, Italy

Location

Fondazione Istituto Neurologico Mondino IRCCS

Pavia, Lombardy, 27100, Italy

Location

AOU Policlinico Giaccone

Palermo, Sicily, 90129, Italy

Location

Fujita Health University Hospital

Aichi, 470-1192, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Gifu University Hospital

Gifu, 501-1194, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Hyogo prefectural Kobe Children's Hospital

Hyogoken, 6500047, Japan

Location

Kobe University Hospital

Hyōgo, 650-0017, Japan

Location

Kagoshima City Hospital

Kagoshima, 890-8760, Japan

Location

St.Marianna University School of Medicine hospital

Kanagawa, 216-8511, Japan

Location

Kitasato University Hospital

Kanagawa, 252-0375, Japan

Location

Tokai University Hospital

Kanagawa, 259-1193, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

The University of Osaka Hospital

Osaka, 565-0871, Japan

Location

Kindai University Hospital

Osaka, 590-0197, Japan

Location

Ageo Central General Hospital

Saitama, 362-8588, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Nihon University Itabashi Hospital

Tokyo, 173-8610, Japan

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Szpital Uniwersytecki w Krakowie

Krakow, 30-688, Poland

Location

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, 02-957, Poland

Location

SPSK nr 1

Zabrze, 41-800, Poland

Location

National University Hospital (NUH)

Singapore, 117599, Singapore

Location

National Neuroscience Institute

Singapore, 308433, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, DUMMY_VALUE, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Regional Universitario de Malaga ? Hospital General

Málaga, 29010, Spain

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 00833, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan City, 333, Taiwan

Location

MeSH Terms

Interventions

satralizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 16, 2022
• Study Start: September 27, 2022
• Primary Completion (Estimated): December 16, 2026
• Study Completion (Estimated): December 14, 2028
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

ES (3); US (17); GH (1); SG (2); NL (1); KR (1); PL (3); AR (3); IT (6); FR (3); TW (2); BR (5); IL (2); CZ (1); JP (18); CN (8); DK (1)