Human Umbilical Cord Mesenchymal Stem Cell-derived ExoSomes for Autoimmune Encephalitis: a Phase I/IIa Clinical Trial (MESAE)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 38
- 主要终点
- DLT events
研究概览
简要总结
This is a phase I/IIa study to investigate the safety and preliminary efficacy of intranasal admnistration of human umbilical mesenchymal stem cell-derived exosome (hUC-MSC-Exo) for patients with autoimmune encephalitis.
详细描述
Dose Escalation Phase:
A multicenter, single-arm, open-label study will be conducted to evaluate the safety, tolerance, and dose exploration of multiple administrations of hUC-MSC-Exo for treating AE. Three dose cohorts (2.5×10¹⁰, 5.0×10¹⁰, and 1.0×10¹¹ particles) will be enrolled with 3-6 subjects each. Administration will be intranasal, once daily for 7 consecutive days, followed by once weekly for 3 consecutive weeks, resulting in a total treatment period of 4 weeks. After the last subject in each cohort completes the final dose and undergoes a 21-day safety assessment, a decision will be made regarding progression to the next higher dose cohort for further evaluation of safety and tolerance. The maximal tolerance dose (MTD) will be determined.
Case Expansion Phase:
A multicenter, randomized, double-blind, placebo-controlled study will enroll 20 subjects randomly assigned to either the experimental group (exosome group) or the control group (exosome mimetic group) in a 1:1 ratio. The dosage for the experimental group will be determined by the Data Safety Monitoring Board (DSMB) based on the safety and efficacy data obtained during the dose exploration phase.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-65 years, both male and female are eligible;
- •Diagnosis of autoimmune encephalitis within 3 months of onset (meeting the 2016 Graus and Dalmau diagnostic criteria), with positive serum/cerebrospinal fluid anti-NMDAR antibodies or anti-LGI1 antibodies;
- •Modified Rankin Scale (mRS) score ≥ 2 at enrollment;
- •The subject or legally authorized representative is able to sign the informed consent form;
- •Subjects of childbearing potential must agree to practice strict contraception during the study period.
排除标准
- •Pre-morbid modified Rankin Scale (mRS) score ≥ 2;
- •Known allergy to any component of the investigational product or history of severe allergic reactions;
- •Presence of neurological or psychiatric disorders (e.g., cerebrovascular disease, Parkinson's disease, severe depression) deemed by the investigator to potentially impair trial participation or study assessments;
- •Current or history of any clinically significant systemic diseases judged by the investigator as unsuitable for inclusion, including but not limited to:
- •Severe cardiovascular diseases (e.g., congestive heart failure, severe arrhythmia, myocardial infarction)
- •Hepatic diseases (e.g., cirrhosis)
- •Renal diseases (e.g., requiring hemodialysis or peritoneal dialysis)
- •Hematological diseases (e.g., hemophilia with bleeding tendency)
- •Endocrine disorders (e.g., poorly controlled diabetes with blood glucose >16.8 mmol/L or <2.8 mmol/L, or with severe complications)
- •Immune system disorders (active or uncontrolled systemic autoimmune diseases, primary/secondary immunodeficiency)
- •Malignancies;
- •Anatomical nasal abnormalities, nasal mucosal damage, severe rhinitis, or other nasal conditions affecting drug administration;
- •Requiring nasogastric tube placement;
- •Organ function meeting any of the following criteria:
- •Absolute neutrophil count (ANC) <1.5×10⁹/L, platelets (PLT) <100×10⁹/L, hemoglobin (Hb) <90 g/L
- •Aspartate aminotransferase (AST) >2.5×ULN and/or alanine aminotransferase (ALT) >2.5×ULN, total bilirubin (TBIL) >1.5×ULN
- •Creatinine >1.5×ULN
- •Without anticoagulant/antiplatelet therapy: International normalized ratio (INR) >1.7 or activated partial thromboplastin time (APTT) >1.25×ULN With anticoagulant/antiplatelet therapy: INR >3.0 or APTT >1.5×ULN;
- •Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable HBV-DNA; or positive for hepatitis C antibody (HCVAb), Treponema pallidum antibody (TPAb/RPR), or human immunodeficiency virus antibody (HIV);
- •Pregnant or lactating patients;
- •Contraindications for MRI (e.g., metal implants such as pacemakers, claustrophobia);
- •Participation in any clinical trial involving investigational drugs within 3 months prior to dosing (or within 5 half-lives of last dose, whichever is longer);
- •Major trauma or surgery within 3 months prior to dosing, or planned surgery during the trial (excluding laparoscopy or minor procedures >4 weeks before baseline; excluding thymoma/teratoma surgery);
- •History of drug abuse or alcoholism within 1 year prior to dosing;
- •Previous treatment with stem cells or derivatives;
- •Any other condition that may increase patient risk or interfere with result interpretation, as determined by the investigator.
研究组 & 干预措施
Exosome group
干预措施: Human umbilical cord mesenchymal stem cell derived exosomes (Biological)
Control group
干预措施: Placebo Control (Other)
结局指标
主要结局
DLT events
时间窗: Within 24 weeks after drug administration
Drug-related dose limiting toxicity (DLT)
mRS
时间窗: 24 weeks ±10 days
modified Ranking Scale (mRS), which ranges from 0 to 6, with higher scores indicating worse outcome, and a score of 6 representing death.
次要结局
- Percentage of mRS improvement ≧ 1(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- MoCA score change compared to baseline(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- mRS(5 weeks (±3 days), 12 weeks (±5 days))
- Percentage of mRS 0-2(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- AE and SAE(Within 24 weeks after drug administration)
- CASE score change compared to baseline(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- ADL score change compared to baseline(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- MMSE score change compared to baseline(5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days))
- Relapse rate of autoimmne encephalits(Within 24 weeks)
研究者
cuilili
Principle investigator
Xuanwu Hospital, Beijing