hUC-MSC-Exo Therapy for Autoimmune Encephalitis (MESAE)

Capital Medical University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Autoimmune Encephalitis

Treatments: Other: Placebo Control; Biological: Human umbilical cord mesenchymal stem cell derived exosomes

Study type: Interventional

Funder types: Other

Identifiers

NCT07131683

BRWEP2024W022010110 (Other Grant/Funding Number)

KS2025069

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 38 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18-65 years, both male and female are eligible;
2. 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;
3. Modified Rankin Scale (mRS) score ≥ 2 at enrollment;
4. The subject or legally authorized representative is able to sign the informed consent form;
5. Subjects of childbearing potential must agree to practice strict contraception during the study period.

Exclusion criteria

1. Pre-morbid modified Rankin Scale (mRS) score ≥ 2;

2. Known allergy to any component of the investigational product or history of severe allergic reactions;

3. 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;

4. 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;

5. Anatomical nasal abnormalities, nasal mucosal damage, severe rhinitis, or other nasal conditions affecting drug administration;

6. Requiring nasogastric tube placement;

7. Organ function meeting any of the following criteria:

   1. Absolute neutrophil count (ANC) <1.5×10⁹/L, platelets (PLT) <100×10⁹/L, hemoglobin (Hb) <90 g/L
   2. Aspartate aminotransferase (AST) >2.5×ULN and/or alanine aminotransferase (ALT) >2.5×ULN, total bilirubin (TBIL) >1.5×ULN
   3. Creatinine >1.5×ULN
   4. 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;

8. 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);

9. Pregnant or lactating patients;

10. Contraindications for MRI (e.g., metal implants such as pacemakers, claustrophobia);

11. 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);

12. 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);

13. History of drug abuse or alcoholism within 1 year prior to dosing;

14. Previous treatment with stem cells or derivatives;

15. Any other condition that may increase patient risk or interfere with result interpretation, as determined by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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38 participants in 2 patient groups, including a placebo group

Exosome group

Experimental group

Treatment:

Biological: Human umbilical cord mesenchymal stem cell derived exosomes

Control group

Placebo Comparator group

Treatment:

Other: Placebo Control