A 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 (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, pharmacokinetics, and pharmacodynamics of satralizumab in participants with anti-N-methyl-D-aspartic acid receptor (NMDAR) and anti-leucine-rich glioma-inactivated 1 (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 Mejia
  • Ciudad Autonoma Bs As, Argentina, C1280AEB
    • Recruiting
    • Hospital Británico
  • San Miguel de Tucuman, Argentina, T4000IDK
    • Recruiting
    • Sanatorio del Sur S.A.
• Austria
  • Linz, Austria, 4020
    • Recruiting
    • Kepler Universitätsklinikum GmbH - Neuromed Campus; Innere Medizin mit Neuroonkologie
  • Wien, Austria, 1090
    • Recruiting
    • Medizinische Universität Wien; Univ.Klinik fuer Neurologie
• Brazil
  • ES
    • Vitoria, ES, Brazil, 29055-450
      • Recruiting
      • CEDOES - Diagnóstico e Pesquisa
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Recruiting
      • Instituto de Neurologia de Curitiba
  • SP
    • Sao Paulo, SP, Brazil, 01228-200
      • Recruiting
      • Centro de Pesquisas Clinicas; CPCLIN
• China
  • Beijing, China, 100730
    • Active, not recruiting
    • Beijing Tongren Hospital
  • Beijing City, China, 100050
    • Recruiting
    • Beijing Tiantan Hospital,Capital Medical University
  • Beijing City, China, 100045
    • Recruiting
    • Beijing Children's hospital, Capital Medical University
  • Changchun City, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Changsha, China, 410011
    • Recruiting
    • The Second Xiangya Hospital of Central South University
  • Chengdu City, China, 610047
    • Recruiting
    • West China Hospital - Sichuan University
  • Fuzhou City, 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 City, China, 200040
    • Recruiting
    • Huashan Hospital, Fudan University
  • Taiyuan, China, 030001
    • Recruiting
    • The First Hospital of Shanxi Medical University
  • Wenzhou City, China, 325035
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan City, China, 430030
    • Recruiting
    • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Recruiting
    • Fakultni Nemocnice Hradec Kralove
  • Praha 5, Czechia, 150 06
    • Recruiting
    • Fakultni nemocnice v Motole; Neurologicka klinika 2. LF UK a FN Motol
• Denmark
  • Odense C, Denmark, 5000
    • Recruiting
    • Odense Universitetshospital, Neurologisk Afdeling N
• France
  • Bron, France, 69677
    • Recruiting
    • Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
  • Tours, France, 37000
    • Recruiting
    • CHRU - Hôpital Bretonneau; Neurologie
• Ghana
  • Kumasi, Ghana
    • Recruiting
    • Komfo Anokye Teaching Hospital; Department of Medicine
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Recruiting
      • A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
    • Napoli, Campania, Italy, 80138
      • Recruiting
      • AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica
  • Lazio
    • Roma, Lazio, Italy, 00165
      • Recruiting
      • Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • Irccs A.O.U.San Martino Ist; Dinogmi
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Recruiting
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Milano, Lombardia, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Pavia, Lombardia, Italy, 27100
      • Recruiting
      • Fondazione Istituto Neurologico Mondino IRCCS
  • Sicilia
    • Palermo, Sicilia, Italy, 90129
      • Recruiting
      • AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla
• Japan
  • Aichi, Japan, 470-1192
    • Recruiting
    • Fujita Health University Hospital
  • Chiba, Japan, 260-8677
    • Recruiting
    • Chiba University Hospital
  • Fukuoka, Japan, 814-0180
    • Recruiting
    • Fukuoka University Hospital
  • Fukuoka, Japan, 812-8582
    • Active, not recruiting
    • Kyushu University Hospital
  • Gifu, Japan, 501-1194
    • Recruiting
    • Gifu University Hospital
  • Hokkaido, Japan, 060-8648
    • Active, not recruiting
    • Hokkaido University Hospital
  • Hyogo, Japan, 650-0017
    • Recruiting
    • Kobe University Hospital
  • Hyogoken, Japan, 6500047
    • Recruiting
    • Hyogo prefectural Kobe Children's Hospital
  • Kanagawa, Japan, 259-1193
    • Recruiting
    • Tokai University Hospital
  • Kanagawa, Japan, 252-0375
    • Active, not recruiting
    • Kitasato University Hospital
  • Kanagawa, Japan, 216-8511
    • Active, not recruiting
    • St.Marianna University School of Medicine hospital; Medical Oncology
  • Miyagi, Japan, 980-8574
    • Recruiting
    • Tohoku University Hospital
  • Osaka, Japan, 565-0871
    • Active, not recruiting
    • Osaka University Hospital
  • Osaka-sayama, Japan, 589-8511
    • Recruiting
    • Kinki University Hospital, Faculty of Medicine
  • Saitama, Japan, 362-8588
    • Recruiting
    • Ageo Central General Hospital
  • Tokyo, Japan, 113-8431
    • Recruiting
    • Juntendo University Hospital
  • Tokyo, Japan, 173-8610
    • Active, not recruiting
    • Nihon University Itabashi Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus MC
• Poland
  • Grudzi?dz, Poland, 86-300
    • Withdrawn
    • Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Neurologiczny
  • Kraków, Poland, 31-503
    • Active, not recruiting
    • Szpital Uniwersytecki w Krakowie; Oddzia? kliniczny Neurologii
  • Warszawa, Poland, 02-957
    • Recruiting
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
  • Zabrze, Poland, 41-800
    • Recruiting
    • SPSK nr 1; Klinika Neurologii
• Taiwan
  • Kaohsiung City, Taiwan, 00833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • North Dist., Taiwan, 40402
    • Recruiting
    • China Medical University Hospital
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital - Linkou
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • Newport Beach, California, United States, 92658
      • Recruiting
      • Hoag Memorial Hospital
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF- Multiple Sclerosis Centre; Department of Neurology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado; Anschutz Medical Campus Department of Neurology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals & Clinics; Department of Neurology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center; Department of Neurology
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Hospital; Neurology
  • 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
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals of Cleveland
    • Cleveland, Ohio, United States, 44915
      • Recruiting
      • Cleveland Clinic Foundation
  • Washington
    • Seattle, Washington, United States, 98122
      • Recruiting
      • 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 autoimmune encephalitis (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 National Medical Products Administration (NMPA)-recognized sites: participants who are current residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry

N-methyl-D-aspartic acid receptor (NMDAR) AIE Cohort

• Age >=12 years
• Diagnosis of probable or definite NMDAR encephalitis

Leucine-rich glioma-inactivated 1 (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 patients 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 GAD-65
• Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1
• 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 IL-6 inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, or bone marrow transplantation
• Any previous treatment with anti-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 IST as background therapy
• Contraindication to all of the following rescue treatments: rituximab, 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 that may preclude patient participation
• Congenital or acquired immunodeficiency, including 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
• Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
• 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
• Laboratory abnormalities at Screening

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 Q4W thereafter. Participants will receive satralizumab according to body weight. Study drug will be administered by 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 Q4W thereafter. Participants will receive satralizumab according to body weight. Study drug will be administered by 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 autoimmune encephalitis (AIE) Placebo cohort; Adults and adolescents with definite or probable NMDAR encephalitis	Other: Placebo; Satralizumab placebo 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 NSD and extended finger flange) filled with 0.5 mL of solution, corresponding to 60 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 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 NSD and extended finger flange) filled with 0.5 mL of solution, corresponding to 60 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	Measure Description	Time Frame
Part 1: Proportion of participants with mRS score improvement ≥ 1 from baseline and no use of rescue therapy at Week 24	mRS = Modified Rankin Scale	Baseline up to Week 24
Part 2: Percentage of participants with adverse events		From Week 52 up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Time to mRS score improvement ≥ 1 from baseline without use of rescue therapy	mRS = Modified Rankin Scale	Baseline up to Week 52
Part 1: Time to rescue therapy		Baseline up to Week 52
Part 1: Time to seizure freedom or cessation of status epilepticus without use of rescue therapy	Seizure freedom defined as a cessation of seizures for at least 6 consecutive weeks	Baseline up to Week 24
Part 1: Change in CASE score from baseline at Week 24	CASE = Clinical Assessment Scale in Autoimmune Encephalitis	Baseline up to Week 24
Part 1: MOCA total score at Week 24	MOCA = Montreal Overall Cognitive Assessment;	Baseline up to Week 24
Part 1: RAVLT score at Week 24 (LGI1 AIE cohort)	RAVLT = Rey Auditory Verbal Learning Test.	Baseline up to Week 24
Part 1: mRS score at Week 24 (as measured on a 7-point scale; NMDAR AIE cohort)	mRS = Modified Rankin Scale	Baseline up to Week 24
Part 1: Percentage of participants with adverse events	Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0	Baseline, Week 52, 2 Years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2022
• Primary Completion (Estimated): June 23, 2025
• Study Completion (Estimated): December 7, 2027

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): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

Drug and device information, study documents

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