Active, not recruiting
Phase 3
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
Condition(s) studied
NMDAR Autoimmune EncephalitisLGI1 Autoimmune Encephalitis
Investigational drug(s) / intervention(s)
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 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.
Placebo: 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 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
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 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
Primary outcome measure(s)
- 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
Trial sites (77)
| Facility | City | Region | Status |
| University of Alabama at Birmingham |
Birmingham |
Alabama |
|
| UC San Diego |
La Jolla |
California |
|
| Hoag Memorial Hospital |
Newport Beach |
California |
|
| UCSF- Multiple Sclerosis Centre |
San Francisco |
California |
|
| University of Colorado |
Aurora |
Colorado |
|
| Childrens National Health Center |
Washington D.C. |
District of Columbia |
|
| Children's Healthcare of Atlanta Center for Advanced Pediatrics |
Atlanta |
Georgia |
|
| University of Maryland Medical Center |
Baltimore |
Maryland |
|
| Johns Hopkins Hospital |
Baltimore |
Maryland |
|
| Brigham and Women's Hospital Department of Neurology |
Boston |
Massachusetts |
|
| Mayo Clinic - Rochester |
Rochester |
Minnesota |
|
| NYU-Langone Medical Center |
New York |
New York |
|
| Duke University Medical Center |
Durham |
North Carolina |
|
| University Hospitals of Cleveland |
Cleveland |
Ohio |
|
| Cleveland Clinic Foundation |
Cleveland |
Ohio |
|
| University of Texas at Houston |
Houston |
Texas |
|
| Medical College of Wisconsin |
Milwaukee |
Wisconsin |
|
| Hospital Ramos Mejía |
CABA |
Argentina |
|
| Hospital Britanico |
Ciudad Autonoma Bs As |
Argentina |
|
| Sanatorio del Sur S.A. |
San Miguel de Tucumán |
Argentina |
|
| Hospital Geral de Fortaleza |
Fortaleza |
Ceará |
|
| CEDOES - Diagnóstico e Pesquisa |
Vitória |
Espírito Santo |
|
| Instituto de Neurologia de Curitiba |
Curitiba |
Paraná |
|
| Centro de Pesquisas Clinicas |
São Paulo |
São Paulo |
|
| Hospital Israelita Albert Einstein |
São Paulo |
São Paulo |
|
| Beijing Children's Hospital, Capital Medical University |
Beijing |
China |
|
| Beijing Tongren Hospital |
Beijing |
China |
|
| Beijing Tiantan Hospital,Capital Medical University |
Beijing |
China |
|
| West China Hospital - Sichuan University |
Chengdu |
China |
|
| Fujian Medical University Union Hospital |
Fuzhou |
China |
|
| Affiliated Hospital of Jining Medical University |
Jining |
China |
|
| Huashan Hospital, Fudan University |
Shanghai |
China |
|
| The First Affiliated Hospital of Wenzhou Medical University |
Wenzhou |
China |
|
| Fakultni nemocnice v Motole |
Prague |
Czechia |
|
| Odense Universitetshospital, Neurologisk Afdeling N |
Odense C |
Denmark |
|
| Hopital neurologique Pierre Wertheimer - CHU Lyon |
Bron |
France |
|
| Hopital Pitié Salpétrière - CHU |
Paris |
France |
|
| CHRU - Hôpital Bretonneau |
Tours |
France |
|
| Komfo Anokye Teaching Hospital |
Kumasi |
Ghana |
|
| Hadassah University Hospital Ein Kerem |
Jerusalem |
Israel |
|
+ 37 more sites — see the full list on the official registry below.
More Hoffmann-La Roche trials in China