Clinical trial NCT05503264: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: NMDAR Autoimmune Encephalitis
LGI1 Autoimmune Encephalitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2022-08-16
Enrollment: 152
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline up to Week 24
measure: 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
timeFrame: Baseline up to Week 52
measure: Part 2: Percentage of Participants With Adverse Events (AEs)
timeFrame: From Week 52 up to 2 years
Secondary outcomes:
measure: Part 1 (NMDAR AIE Cohort and LGI1 Cohort): Time to mRS Score Improvement ≥ 1 From Baseline Without Use of Rescue Therapy
timeFrame: Baseline up to Week 52
measure: Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Time to Rescue Therapy
timeFrame: Baseline up to Week 52
measure: Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Proportion of Participants With Sustained Seizure Cessation at Week 24
timeFrame: Baseline up to Week 24
measure: Part 1 (NMDAR AIE Cohort): Change in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score From Baseline at Week 24
timeFrame: Baseline up to Week 24
measure: Part 1 (LGI1 AIE Cohort): Change in CASE Score From Baseline at Week 52
timeFrame: Baseline up to Week 52
measure: Part 1 (NMDAR AIE Cohort): Montreal Overall Cognitive Assessment (MOCA) Total Score at Week 24
timeFrame: Baseline up to Week 24
measure: Part 1 (LGI1 AIE Cohort): MOCA Total Score at Week 52
timeFrame: Baseline up to Week 52
measure: Part 1 (LGI1 AIE Cohort): Rey Auditory Verbal Learning Test (RAVLT) Score at Week 52
timeFrame: Baseline up to Week 52
measure: Part 1 (NMDAR AIE Cohort): mRS Score at Week 24 (as Measured on a 7-point Scale)
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants With AEs
timeFrame: Baseline, Week 52, 2 Years
measure: Parts 1 and 2: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: San Francisco
country: United States
facility: UCSF- Multiple Sclerosis Centre
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital Department of Neurology
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: NYU-Langone Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania Med Ctr
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas at Houston
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Caba
country: Argentina
facility: Hospital Ramos Mejía
city: Ciudad Autonoma Bs As
country: Argentina
facility: Hospital Britanico
city: San Miguel de Tucuman
country: Argentina
facility: Sanatorio del Sur S.A.
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH - Neuromed Campus
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza
state: Ceará
city: Vitoria
country: Brazil
facility: CEDOES - Diagnóstico e Pesquisa
state: Espírito Santo
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba
state: Paraná
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisas Clinicas
state: São Paulo
city: Beijing City
country: China
facility: Beijing Children's Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Beijing
country: China
facility: Beijing Tiantan Hospital,Capital Medical University
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu City
country: China
facility: West China Hospital - Sichuan University
city: Fuzhou City
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Guangzhou First Municipal People's Hospital
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
city: Shanghai City
country: China
facility: Huashan Hospital, Fudan University
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
city: Wenzhou City
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan City
country: China
facility: Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Neurologisk Afdeling N
city: Bron
country: France
facility: Hopital neurologique Pierre Wertheimer - CHU Lyon
city: Paris
country: France
facility: Hopital Pitié Salpétrière - CHU
city: Saint Etienne
country: France
facility: CHU Saint Etienne - Hôpital Nord
city: Tours
country: France
facility: CHRU - Hôpital Bretonneau
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital
city: Napoli
country: Italy
facility: A. O. U. Federico II
state: Campania
city: Napoli
country: Italy
facility: AOU Seconda Università degli Studi
state: Campania
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Genova
country: Italy
facility: Irccs A.O.U.San Martino Ist
state: Liguria
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Mondino IRCCS
state: Lombardia
city: Palermo
country: Italy
facility: AOU Policlinico Giaccone
state: Sicilia
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogoken
country: Japan
facility: Hyogo prefectural Kobe Children's Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital
city: Kanagawa
country: Japan
facility: St.Marianna University School of Medicine hospital
city: Kanagawa
country: Japan
facility: Kitasato University Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Osaka-sayama
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: The University of Osaka Hospital
city: Saitama
country: Japan
facility: Ageo Central General Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Grudzi?dz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. W. Bieganskiego
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
city: Zabrze
country: Poland
facility: SPSK nr 1
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: North Dist.
country: Taiwan
facility: China Medical University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: