hUC-MSC-Exo Therapy for Autoimmune Encephalitis

Official title

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

Overview

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.

Detailed 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.

Interventions

• Biological 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
• Other Placebo Control
  Nasal spray of placebo control, once per day for 7 days, then once per week for 3 weeks

Primary outcome measures

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

Secondary outcome measures (9)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07131683 · KS2025069 · BRWEP2024W022010110

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗