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
- Conditions
- NMDAR Autoimmune EncephalitisLGI1 Autoimmune Encephalitis
- Interventions
- Other: Placebo
- Registration Number
- NCT05503264
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 152
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LGI1 AIE Placebo Cohort Placebo Adults with LGI1 encephalitis NMDAR Autoimmune Encephalitis (AIE) Cohort Satralizumab Adults and adolescents with definite or probable NMDAR encephalitis LGI1 AIE Cohort Satralizumab Adults with LGI1 encephalitis NMDAR AIE Placebo Cohort Placebo Adults and adolescents with definite or probable NMDAR encephalitis
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Sustained seizure cessation is defined as 4 consecutive weeks of no seizures maintained until Week 24 and no use of rescue therapy.
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 Baseline, Week 52, 2 Years Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5.0)
Parts 1 and 2: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Baseline up to 2 years 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.
Trial Locations
- Locations (81)
SPSK nr 1
🇵🇱Zabrze, Poland
Regionalny Szpital Specjalistyczny im. W. Bieganskiego
🇵🇱Grudzi?dz, Poland
Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Poland
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UC San Diego
🇺🇸La Jolla, California, United States
Hoag Memorial Hospital
🇺🇸Newport Beach, California, United States
UCSF- Multiple Sclerosis Centre
🇺🇸San Francisco, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital Department of Neurology
🇺🇸Boston, Massachusetts, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
NYU-Langone Medical Center
🇺🇸New York, New York, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Univ of Pennsylvania Med Ctr
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas at Houston
🇺🇸Houston, Texas, United States
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hospital Ramos Mejía
🇦🇷Caba, Argentina
Hospital Britanico
🇦🇷Ciudad Autonoma Bs As, Argentina
Sanatorio del Sur S.A.
🇦🇷San Miguel de Tucuman, Argentina
Kepler Universitätsklinikum GmbH - Neuromed Campus
🇦🇹Linz, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
CEDOES - Diagnóstico e Pesquisa
🇧🇷Vitoria, Espírito Santo, Brazil
Instituto de Neurologia de Curitiba
🇧🇷Curitiba, Paraná, Brazil
Centro de Pesquisas Clinicas
🇧🇷Sao Paulo, São Paulo, Brazil
Beijing Children's Hospital, Capital Medical University
🇨🇳Beijing City, China
Beijing Tongren Hospital
🇨🇳Beijing, China
Beijing Tiantan Hospital,Capital Medical University
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, China
West China Hospital - Sichuan University
🇨🇳Chengdu City, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou City, China
Guangzhou First Municipal People's Hospital
🇨🇳Guangzhou, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, China
Huashan Hospital, Fudan University
🇨🇳Shanghai City, China
The First Hospital of Shanxi Medical University
🇨🇳Taiyuan, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou City, China
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Odense Universitetshospital, Neurologisk Afdeling N
🇩🇰Odense C, Denmark
Hopital neurologique Pierre Wertheimer - CHU Lyon
🇫🇷Bron, France
Hopital Pitié Salpétrière - CHU
🇫🇷Paris, France
CHU Saint Etienne - Hôpital Nord
🇫🇷Saint Etienne, France
CHRU - Hôpital Bretonneau
🇫🇷Tours, France
Komfo Anokye Teaching Hospital
🇬🇭Kumasi, Ghana
A. O. U. Federico II
🇮🇹Napoli, Campania, Italy
AOU Seconda Università degli Studi
🇮🇹Napoli, Campania, Italy
Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
🇵🇱Warszawa, Poland
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Lazio, Italy
Irccs A.O.U.San Martino Ist
🇮🇹Genova, Liguria, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Lombardia, Italy
Fondazione Istituto Neurologico Mondino IRCCS
🇮🇹Pavia, Lombardia, Italy
AOU Policlinico Giaccone
🇮🇹Palermo, Sicilia, Italy
Fujita Health University Hospital
🇯🇵Aichi, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Gifu University Hospital
🇯🇵Gifu, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Hyogo prefectural Kobe Children's Hospital
🇯🇵Hyogoken, Japan
Kobe University Hospital
🇯🇵Hyogo, Japan
Kagoshima City Hospital
🇯🇵Kagoshima, Japan
St.Marianna University School of Medicine hospital
🇯🇵Kanagawa, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Kindai University Hospital
🇯🇵Osaka-sayama, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Ageo Central General Hospital
🇯🇵Saitama, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Erasmus MC
🇳🇱Rotterdam, Netherlands
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
China Medical University Hospital
🇨🇳North Dist., Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan City, Taiwan