NMDAR Autoimmune EncephalitisPhase 3CieloNCT05503264
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
A Phase 3 study testing Satralizumab in people with NMDAR Autoimmune Encephalitis and LGI1 Autoimmune Encephalitis, run by Hoffmann-La Roche at 56 sites in 15 countries.
Trial summary
The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- NMDAR Autoimmune Encephalitis, LGI1 Autoimmune Encephalitis
- What is being tested?
- Satralizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 56 sitesin 15 countries
- Study dates
- 27 Sep 2022to 14 Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- Age ≥ 12 years
- Diagnosis of probable or definite NMDAR encephalitis
- LGI1 AIE Cohort
- Age ≥ 18 years
- Diagnosis of LGI1 encephalitis
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
56 sites in 15 countries.
56 sites in 15 countries
Japan12 sites
Fujita Health University Hospital
Aichi, 470-1192
Chiba University Hospital
Chiba, 260-8677
Kyushu University Hospital
Fukuoka, 812-8582
Gifu University Hospital
Gifu, 501-1194
Hokkaido University Hospital
Hokkaido, 060-8648
Kobe University Hospital
Hyōgo, 650-0017
St.Marianna University School of Medicine hospital
Kanagawa, 216-8511
Kitasato University Hospital
Kanagawa, 252-0375
Tokai University Hospital
Kanagawa, 259-1193
Tohoku University Hospital
Miyagi, 980-8574
The University of Osaka Hospital
Osaka, 565-0871
Nihon University Itabashi Hospital
Tokyo, 173-8610
United States11 sites
University of Colorado
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Brigham and Women's Hospital Department of Neurology
Boston, Massachusetts, 02115
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44915
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
NYU-Langone Medical Center
New York, New York, 10016
Hoag Memorial Hospital
Newport Beach, California, 92658
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
UCSF- Multiple Sclerosis Centre
San Francisco, California, 94158
Childrens National Health Center
Washington D.C., District of Columbia, 20010
China8 sites
Beijing Children's Hospital, Capital Medical University
Beijing, 100045
Beijing Tongren Hospital
Beijing, 100730
Beijing Tiantan Hospital,Capital Medical University
Beijing
West China Hospital - Sichuan University
Chengdu, 610047
Fujian Medical University Union Hospital
Fuzhou, 350001
Affiliated Hospital of Jining Medical University
Jining, 272029
Huashan Hospital, Fudan University
Shanghai, 200040
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, 325035
Brazil5 sites
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310
Hospital Geral de Fortaleza
Fortaleza, Ceará, 60175-295
Centro de Pesquisas Clinicas
São Paulo, São Paulo, 01228-200
Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05652-000
CEDOES - Diagnóstico e Pesquisa
Vitória, Espírito Santo, 29055-450
Italy4 sites
Irccs A.O.U.San Martino Ist
Genoa, Liguria, 16132
A. O. U. Federico II
Naples, Campania, 80131
AOU Policlinico Giaccone
Palermo, Sicily, 90129
Fondazione Istituto Neurologico Mondino IRCCS
Pavia, Lombardy, 27100
Argentina3 sites
Hospital Ramos Mejía
CABA, C1221ADC
Hospital Britanico
Ciudad Autonoma Bs As, C1280AEB
Sanatorio del Sur S.A.
San Miguel de Tucumán, T4000IDK
France2 sites
Hopital neurologique Pierre Wertheimer - CHU Lyon
Bron, 69677
Hopital Pitié Salpétrière - CHU
Paris, 75651
Israel2 sites
Hadassah University Hospital Ein Kerem
Jerusalem, 9112001
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
Poland2 sites
Szpital Uniwersytecki w Krakowie
Krakow, 30-688
SPSK nr 1
Zabrze, 41-800
Taiwan2 sites
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 00833
Chang Gung Memorial Hospital - Linkou
Taoyuan City, 333
Denmark1 site
Odense Universitetshospital, Neurologisk Afdeling N
Odense C, 5000
About this study
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
The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis.
- Being tested
- Satralizumab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SatralizumabDrug
Also called Enspryng; RO5333787
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Satralizumab |
| LGI1 AIE Cohort | Experimental | Adults with LGI1 encephalitis as per the schedule specified in the protocol. Receives: 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. Receives: Other: Placebo |
| LGI1 AIE Placebo Cohort | Placebo comparator | Adults with LGI1 encephalitis will receive satralizumab placebo as per the schedule specified in the protocol. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline up to Week 52
Part 2: Percentage of Participants With Adverse Events (AEs)
Measured: 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
Measured: Baseline up to Week 52
Part 1 (NMDAR AIE Cohort and LGI1 AIE Cohort): Time to Rescue Therapy
Measured: 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.
Measured: 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
Measured: Baseline up to Week 24
Part 1 (LGI1 AIE Cohort): Change in CASE Score From Baseline at Week 52
Measured: Baseline up to Week 52
Part 1 (NMDAR AIE Cohort): Montreal Overall Cognitive Assessment (MOCA) Total Score at Week 24
Measured: Baseline up to Week 24
Part 1 (LGI1 AIE Cohort): MOCA Total Score at Week 52
Measured: Baseline up to Week 52
Part 1 (LGI1 AIE Cohort): Rey Auditory Verbal Learning Test (RAVLT) Score at Week 52
Measured: Baseline up to Week 52
Part 1 (NMDAR AIE Cohort): mRS Score at Week 24 (as Measured on a 7-point Scale)
Measured: 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)
Measured: Baseline up to Week 52
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.
Measured: Baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start27 Sep 2022
- Primary completion16 Dec 2026 (estimated)
- Study completion14 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NMDAR Autoimmune EncephalitisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05503264
- Sponsor's protocol ID
- WN43174
- Other IDs
- 2021-002395-39, 2023-504226-18-00, 2023
- Acronym
- Cielo
- Status last verified
- Oct 2026
- First submitted
- 15 Aug 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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