NCT05503264进行中（未招募）3 期
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
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 122
- 试验地点
- 147
- 主要终点
- 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
研究概览
简要总结
The purpose of this study is to assess the efficacy, safety, PK, and PD of satralizumab in participants with NMDAR and LGI1 encephalitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Satralizumab (Drug)
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.
干预措施: Placebo (Other)
LGI1 AIE Placebo Cohort
Placebo Comparator
Adults with LGI1 encephalitis will receive satralizumab placebo as per the schedule specified in the protocol.
干预措施: Placebo (Other)
LGI1 AIE Cohort
Experimental
Adults with LGI1 encephalitis as per the schedule specified in the protocol.
干预措施: Satralizumab (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: Baseline up to Week 52
Part 2: Percentage of Participants With Adverse Events (AEs)
时间窗: From Week 52 up to 2 years
次要结局
- 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)
- Parts 1 and 2: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline up to 2 years)
- Part 1 (LGI1 AIE Cohort): Change in CASE Score From Baseline at Week 52(Baseline up to Week 52)
- 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)
- 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 (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)
研究者
研究点 (147)
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