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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
38
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
Nasal spray of placebo control, once per day for 7 days, then once per week for 3 weeks
DLT events
Drug-related dose limiting toxicity (DLT)
Time frame: Within 24 weeks after drug administration
mRS
modified Ranking Scale (mRS), which ranges from 0 to 6, with higher scores indicating worse outcome, and a score of 6 representing death.
Time frame: 24 weeks ±10 days
AE and SAE
Adverse events and severe adverse events
Time frame: Within 24 weeks after drug administration
mRS
modified Ranking Scale (mRS), which ranges from 0 to 6, with higher scores indicating worse outcome, and a score of 6 representing death.
Time frame: 5 weeks (±3 days), 12 weeks (±5 days)
Percentage of mRS 0-2
Percentage of mRS 0-2. modified Ranking Scale (mRS), which ranges from 0 to 6, with higher scores indicating worse outcome, and a score of 6 representing death.
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
Percentage of mRS improvement ≧ 1
Percentage of mRS improvement ≧ 1. modified Ranking Scale (mRS), which ranges from 0 to 6, with higher scores indicating worse outcome, and a score of 6 representing death.
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
CASE score change compared to baseline
Clinical Assessment Scale in Autoimmune Encephalitis (CASE), ranging from 0 to 27 points, with higher score indicating more severe symptoms
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
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ADL score change compared to baseline
Activity of daily living (ADL) score, ranging from 0 to 100, with higher score indicating better daily living abilities
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
MMSE score change compared to baseline
mini-mental state examination (MMSE), ranging from 0 to 30, with higher score indicating better cognition
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
MoCA score change compared to baseline
Montreal Cognitive Assessment Scale (MoCA), ranging from 0 to 30, with higher score indicating better cognition
Time frame: 5 weeks (±3 days), 12 weeks (±5 days), 24 weeks (±10 days)
Relapse rate of autoimmne encephalits
Time frame: Within 24 weeks