hUC-MSC-Exo Therapy for Autoimmune Encephalitis

Официальное название

Human Umbilical Cord Mesenchymal Stem Cell-derived ExoSomes for Autoimmune Encephalitis: a Phase I/IIa Clinical Trial (MESAE)

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Human umbilical cord mesenchymal stem cell derived exosomes
  Nasal spray of hUC-MSC-Exo (low dose: 2.5×10\^10 particles, mid-dose: 5.0×10\^10 particles, high-dose: 1.0×10\^11 particles), once per day for 7 days, then once per week for 3 weeks
• Другое Placebo Control
  Nasal spray of placebo control, once per day for 7 days, then once per week for 3 weeks

Первичные конечные точки

• DLT events [Срок оценки: Within 24 weeks after drug administration]
• mRS [Срок оценки: 24 weeks ±10 days]

Вторичные конечные точки (9)

• AE and SAE [Срок оценки: Within 24 weeks after drug administration]
• mRS [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days)]
• Percentage of mRS 0-2 [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• Percentage of mRS improvement ≧ 1 [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• CASE score change compared to baseline [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• ADL score change compared to baseline [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• MMSE score change compared to baseline [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• MoCA score change compared to baseline [Срок оценки: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)]
• Relapse rate of autoimmne encephalits [Срок оценки: Within 24 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07131683 · KS2025069 · BRWEP2024W022010110

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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