Safety and Efficacy of Human Adipose-Derived Stem Cell Exosomes in Acute Ischemic Stroke

Clinical Study on the Safety and Efficacy of Human Adipose-Derived Stem Cell Exosomes in the Treatment of Acute Ischemic Stroke

This is a Phase I/II, randomized, double-blind, placebo-controlled, single/multiple ascending dose clinical study (Investigator-Initiated Trial, IIT) evaluating the safety and efficacy of Human Adipose-Derived Stem Cell Exosomes (ADSC-exo, STX11102 Nasal Spray) in treating acute ischemic stroke (AIS). The study consists of two sequential parts: a Single-Ascending Dose (SAD) study and a Multiple-Ascending Dose (MAD) study.

The SAD part will enroll 12 subjects with mild stroke (NIHSS 1-4). They will be sequentially enrolled into three dose cohorts (4 subjects each: 2×10⁹, 4×10⁹, and 8×10⁹ particles/mL) to receive a single nasal spray dose alongside standard care, with safety monitoring for 14 days. Dose escalation is contingent upon the safety review of the preceding cohort.

Upon confirming safety, the study proceeds to the MAD part, which will enroll 48 subjects with moderate stroke (NIHSS 5-12). They will be randomized into two dose groups (Low and High Dose), each containing an active treatment arm and a placebo arm (saline) in a 2:1 ratio (16 active:8 placebo per group). Subjects will self-administer the nasal spray daily for 14 days, with follow-up until Day 90. The primary objective is to evaluate safety, with secondary objectives assessing efficacy via neurological function scales (NIHSS, mRS, BI) and infarct volume change on MRI.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Biological: Human Adipose-Derived Stem Cell Exosomes; Other: Placebo

Detailed Description

This clinical trial is designed to investigate the novel therapeutic agent Human Adipose-Derived Stem Cell Exosomes (ADSC-exo, STX11102) delivered via nasal spray for patients with acute ischemic stroke (AIS). The rationale is based on promising preclinical data demonstrating that intranasally administered ADSC-exo can cross the blood-brain barrier, modulate neuroinflammation, reduce infarct volume, and promote functional recovery in animal stroke models.

Study Design and Phases:

The trial employs a two-part, early-phase exploratory design integrating dose-finding and preliminary efficacy assessment.

Part 1: Single-Ascending Dose (SAD) Study: This is an open-label, dose-escalation phase to assess initial safety and tolerability. Twelve subjects with mild AIS (NIHSS 1-4, onset within 72 hours) will be enrolled at a single center. Three dose levels will be tested sequentially: Dose Cohort 1 (2×10⁹ particles/mL), Cohort 2 (4×10⁹ particles/mL), and Cohort 3 (8×10⁹ particles/mL), with 4 subjects per cohort. All subjects will receive a single dose of ADSC-exo nasal spray plus standard care. Escalation to the next higher dose cohort requires completion of the 14-day safety observation for all subjects in the current cohort and a formal safety review by the Principal Investigator (PI) and the sponsor. Escalation is permitted only if the number of subjects experiencing Grade ≥3 adverse events (AEs) considered related to the study drug is ≤50% (i.e., ≤2 subjects) within the completed cohort.

Part 2: Multiple-Ascending Dose (MAD) Study: This is a randomized, double-blind, placebo-controlled, dose-expansion phase to further evaluate safety and explore efficacy. Forty-eight subjects with moderate AIS (NIHSS 5-12, onset within 72 hours) will be enrolled across approximately five centers. Entry into this part requires a favorable safety review of all data from the SAD part. Subjects will be randomized into two sequential dose groups (Low Dose and High Dose). The specific doses (X and Y ×10⁹ particles/mL) for the MAD part will be determined based on SAD results. Each dose group consists of 24 subjects randomized in a 2:1 ratio to receive either ADSC-exo nasal spray (n=16) or matching placebo (saline, n=8) daily for 14 days, in addition to standard care. The Low Dose group must complete enrollment and 14-day safety follow-up before the High Dose group begins enrollment, applying the same safety criteria (≤50% of subjects with related Grade ≥3 AEs) for progression.

Study Population: Key inclusion criteria: age 18-80, anterior circulation ischemic stroke, pre-stroke mRS ≤1. Key exclusion criteria: severe stroke (NIHSS >12), lacunar/brainstem/cerebellar infarct, need for endovascular intervention, intracranial hemorrhage, malignancy, immunodeficiency, significant hepatic/renal impairment, active severe infection, and positive serology for HIV, HBV (with positive DNA), HCV, or syphilis.

Endpoints:

Primary Safety Endpoints: Incidence, severity, and causality of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs); changes in nasal mucosa, pulmonary function, and immunoglobulins.

Secondary Efficacy Endpoints:

SAD: Change from baseline in NIHSS, mRS, and Barthel Index (BI) at Day 14.

MAD: Change in NIHSS at Day 14; change in mRS and BI at Days 7, 14, 30, and 90; change in cerebral infarct lesion volume on MRI at Day 90.

Exploratory Endpoints (MAD): Changes in inflammatory cytokines (IL-2, IL-6, IL-12, IL-1β, TNF-α, IFN-γ).

Study Procedures: The schedule includes a 7-day screening period, treatment period (1 day for SAD, 14 days for MAD), and a follow-up period (14 days for SAD, 76 days for MAD). Assessments include neurological scales (NIHSS, mRS, BI), laboratory tests, vital signs, ECGs, MRI, and pulmonary function tests.

Statistical Analysis: This is an exploratory study with a sample size based on clinical practice. Safety will be analyzed in the Safety Set (SS). Efficacy will be analyzed descriptively for the SAD part. For the MAD part, efficacy will be analyzed in the Full Analysis Set (FAS) and Intent-to-Treat (ITT) set using appropriate statistical models (e.g., ANCOVA for continuous endpoints, Cochran-Mantel-Haenszel test for

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xia Liu, M.D., Ph.D.; Phone Number: 86+19121579288; Email: liuxia6700@163.com
• Study Contact Backup: Name: Ming Zhang; Phone Number: 86+17826520869; Email: zhangming@stexo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 years, male or female
2. Patients with acute ischemic stroke within 72 hours of symptom onset
3. Internal carotid artery system stroke
4. For the single-dose study: mild stroke patients (NIHSS score 1-4, inclusive of 1 and 4)
5. For the multiple-dose study: moderate stroke patients (NIHSS score 5-12, inclusive of 5 and 12)
6. Pre-stroke mRS score ≤ 1
7. Subjects or their guardians voluntarily sign the informed consent form

Exclusion Criteria:

1. Moderate or severe stroke (NIHSS score > 12).
2. Lacunar infarction, brainstem or cerebellar infarction (confirmed by DWI-MRI).
3. Requirement for endovascular interventional treatment for the current episode.
4. Intracranial hemorrhagic diseases (including parenchymal, intraventricular, subarachnoid hemorrhage, etc.).
5. Patients with malignant tumors.
6. Patients with severe traumatic brain injury.
7. Patients with primary or secondary immunodeficiency diseases or requiring immunosuppressant medication.
8. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times the upper limit of normal.
9. Chronic kidney disease or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m².
10. Presence of severe infection or fever; patients with severe respiratory diseases.
11. Positive for hepatitis B virus surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) with positive HBV-DNA; or positive for hepatitis C virus antibody (HCVAb), Treponema pallidum antibody (TPAb/RPR), or human immunodeficiency virus antibody (HIV).
12. Patients who are pregnant or lactating at screening, or wish to become pregnant during the study period. Patients allergic to the product
13. Patients allergic to the product or with severe allergic constitution.
14. Patients deemed unsuitable for participation by the investigator, or for whom participation may pose a greater risk.
15. Patients who have participated in another clinical trial within the past 3 months.
16. Patients with prior use of exosomes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose Study Cohort 1; This is an open-label, single-dose cohort in the dose-escalation phase (Part 1). Four (4) subjects with acute ischemic stroke will receive a single dose of Human Adipose-Derived Stem Cell Exosomes (ADSC-exo) Nasal Spray at a concentration of 2×10^9 particles per mL (total volume 1 mL), administered intranasally once.	Biological: Human Adipose-Derived Stem Cell Exosomes; This intervention involves the use of allogeneic Human Adipose-Derived Stem Cell Exosomes (ADSC-exo), provided as a sterile nasal spray (STX11102).
Experimental: Single Ascending Dose Study Cohort 2; This is an open-label, single-dose cohort in the dose-escalation phase (Part 1). Four (4) subjects with acute ischemic stroke will receive a single dose of Human Adipose-Derived Stem Cell Exosomes (ADSC-exo) Nasal Spray at a concentration of 4×10^9 particles per mL (total volume 1 mL), administered intranasally once.	Biological: Human Adipose-Derived Stem Cell Exosomes; This intervention involves the use of allogeneic Human Adipose-Derived Stem Cell Exosomes (ADSC-exo), provided as a sterile nasal spray (STX11102).
Experimental: Single Ascending Dose Study Cohort 3; This is an open-label, single-dose cohort in the dose-escalation phase (Part 1). Four (4) subjects with acute ischemic stroke will receive a single dose of Human Adipose-Derived Stem Cell Exosomes (ADSC-exo) Nasal Spray at a concentration of 8×10^9 particles per mL (total volume 1 mL), administered intranasally once.	Biological: Human Adipose-Derived Stem Cell Exosomes; This intervention involves the use of allogeneic Human Adipose-Derived Stem Cell Exosomes (ADSC-exo), provided as a sterile nasal spray (STX11102).
Experimental: Multiple Dose Study Low-Dose ADSC-exo (X); This is a double-blind, multiple-dose treatment arm in the dose-expansion phase (Part 2). Sixteen (16) subjects with acute ischemic stroke will receive Human Adipose-Derived Stem Cell Exosomes (ADSC-exo) Nasal Spray at a low concentration (designated as X ×10^9 particles per mL, to be determined based on SAD results), administered intranasally once daily (QD) for 14 consecutive days. This is administered in addition to standard of care (SOC). This arm is compared to a placebo control arm within the same low-dose group.	Biological: Human Adipose-Derived Stem Cell Exosomes; This intervention involves the use of allogeneic Human Adipose-Derived Stem Cell Exosomes (ADSC-exo), provided as a sterile nasal spray (STX11102).
Placebo Comparator: Multiple Dose Study Low-Dose Placebo; This is a double-blind, multiple-dose control arm in the dose-expansion phase (Part 2). Eight (8) subjects with acute ischemic stroke will receive a matching Placebo Nasal Spray (0.9% physiological saline), administered intranasally once daily (QD) for 14 consecutive days. This is administered in addition to standard of care (SOC). This arm serves as the comparator for the active low-dose ADSC-exo arm.	Other: Placebo; This intervention serves as the placebo control. It is a sterile 0.9% sodium chloride (normal saline) solution formulated as a nasal spray
Experimental: Multiple Dose Study High-Dose ADSC-exo (Y); This is a double-blind, multiple-dose treatment arm in the dose-expansion phase (Part 2). Sixteen (16) subjects with acute ischemic stroke will receive Human Adipose-Derived Stem Cell Exosomes (ADSC-exo) Nasal Spray at a high concentration (designated as Y ×10^9 particles per mL, to be determined based on SAD results), administered intranasally once daily (QD) for 14 consecutive days. This is administered in addition to standard of care (SOC). This arm is compared to a placebo control arm within the same high-dose group. Enrollment into this high-dose group is contingent upon a safety review of the low-dose group.	Biological: Human Adipose-Derived Stem Cell Exosomes; This intervention involves the use of allogeneic Human Adipose-Derived Stem Cell Exosomes (ADSC-exo), provided as a sterile nasal spray (STX11102).
Placebo Comparator: Multiple Dose Study High-Dose Placebo; This is a double-blind, multiple-dose control arm in the dose-expansion phase (Part 2). Eight (8) subjects with acute ischemic stroke will receive a matching Placebo Nasal Spray (0.9% physiological saline), administered intranasally once daily (QD) for 14 consecutive days. This is administered in addition to standard of care (SOC). This arm serves as the comparator for the active high-dose ADSC-exo arm.	Other: Placebo; This intervention serves as the placebo control. It is a sterile 0.9% sodium chloride (normal saline) solution formulated as a nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.	Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs): The incidence, severity (graded per CTCAE v5.0), and the investigator-assessed causality (relationship to the study drug) of all AEs and SAEs occurring during the treatment and follow-up period.	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.	Specific Safety Assessments: Nasal Mucosa: Changes from baseline based on physical examination of the nasal cavity.	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.	Specific Safety Assessments: pulmonary function: Changes in FVC versus baseline	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke	Specific Safety Assessments: pulmonary function: Changes in FEV versus baseline	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke	Specific Safety Assessments: pulmonary function: Changes in PEF versus baseline	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.	Immunoglobulins: Changes from baseline in serum levels of IgA.	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.	Immunoglobulins: Changes from baseline in serum levels of IgE	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke	Immunoglobulins: Changes from baseline in serum levels of IgM.	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke	Immunoglobulins: Changes from baseline in serum levels of IgG.	For Single-Dose Study: From first dose on Day 1 through the end of safety follow-up at Day 14. For Multiple-Dose Study: From first dose on Day 1 through the end of safety follow-up, which extends up to 14 days after the last dose on Day 14.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neurological Function (For Single-Dose Study)	This outcome measures the effect of a single dose of ADSC-exo on neurological recovery in patients with mild acute ischemic stroke (NIHSS 1-4). The change from baseline will be assessed using three validated clinical scales at Day 14 post-dose: the National Institutes of Health Stroke Scale (NIHSS) for stroke severity.The scoring range is 0-42 points, with higher scores indicating more severe nerve damage.	Baseline (Day 1, pre-dose) to Day 14 post-dose.
Change in NIHSS Score after 14-Day Treatment (For Multiple-Dose Study)	This outcome measures the change in stroke severity after 14 days of multiple-dose treatment with ADSC-exo in patients with moderate acute ischemic stroke (NIHSS 5-12). The National Institutes of Health Stroke Scale (NIHSS) score will be compared from baseline (Day 1) to the end of the 14-day treatment period (Day 14). A decrease in NIHSS score indicates an improvement in neurological deficit.The scoring range is 0-42 points, with higher scores indicating more severe nerve damage.	Baseline (Day 1, pre-dose) to Day 14 (end of treatment).
Change in Disability & Daily Function (For Multiple-Dose Study)	This outcome measures the sustained effect of multiple-dose ADSC-exo treatment on global disability and daily living function over time. The change from baseline will be assessed using the modified Rankin Scale (mRS) for disability and the Barthel Index (BI) for activities of daily living at multiple timepoints: Day 7, Day 14, Day 30, and Day 90. Lower mRS scores(The scoring range is 0-6 points) and higher BI scores(The scoring range is 0-100 points) indicate better functional outcomes.	Baseline (Day 1, pre-dose) to Day 7, Day 14, Day 30, and Day 90.
Change in Cerebral Infarct Volume on MRI (For Multiple-Dose Study)	This outcome is an imaging-based measure of treatment efficacy. It assesses the change in the volume of the cerebral infarct lesion from baseline (pre-treatment) to 90 days after the start of treatment (Day 90) using Magnetic Resonance Imaging (MRI). A reduction in infarct volume is hypothesized to correlate with neurological recovery and is a key structural endpoint.	Baseline MRI (within screening period, Day -7 to -1) to Day 90 MRI.
Change in Neurological Function (For Single-Dose Study)	This outcome measures the effect of a single dose of ADSC-exo on neurological recovery in patients with mild acute ischemic stroke (NIHSS 1-4). The change from baseline will be assessed using the validated clinical scales at Day 14 post-dose: the modified Rankin Scale (mRS) for global disability.The scoring range is 0-6 points, with higher scores indicating more severe nerve damage.	Baseline (Day 1, pre-dose) to Day 14 post-dose.
Change in Neurological Function (For Single-Dose Study)	This outcome measures the effect of a single dose of ADSC-exo on neurological recovery in patients with mild acute ischemic stroke (NIHSS 1-4). The change from baseline will be assessed using the validated clinical scales at Day 14 post-dose:the Barthel Index (BI) for activities of daily living. The scoring range is 0-100 points, with higher BI scores indicate better functional outcomes.	Baseline (Day 1, pre-dose) to Day 14 post-dose.

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai 10th People's Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; First Affiliated Hospital of the Chinese People's Liberation Army Naval Medical University

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: December 30, 2025
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: acute ischemic stroke; NIHSS; mRS; exosome; human adipose-derived stem cell
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: IIT-ATMP-2025011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will share de-identified individual participant data (IPD) that underlies the results reported in the primary and secondary outcome publications. This will include baseline characteristics (e.g., age, sex, NIHSS score at entry, pre-stroke mRS), treatment assignment (dose group), and outcome data for all primary and secondary endpoints. Specifically, shared data will encompass safety endpoints (all recorded Treatment-Emergent Adverse Events, Serious Adverse Events, and changes in nasal mucosa, pulmonary function, and immunoglobulins) and efficacy endpoints (serial assessments of NIHSS, mRS, Barthel Index scores, and cerebral infarct volume change on MRI at Day 90 for the MAD part). All shared data will be fully anonymized to protect participant confidentiality.
• IPD Sharing Time Frame: The de-identified IPD, study protocol, SAP, and ICF will become available 12 months after the publication of the primary study results (anticipated around September 2029, based on the Study Completion date of August 31, 2028). The data will be accessible for a period of 5 years thereafter (anticipated until September 2034). Requests can be submitted during this 5-year window.
• IPD Sharing Access Criteria: Access will be granted to qualified researchers from accredited scientific or medical institutions for the purpose of conducting analyses to achieve pre-specified research goals in the approved proposal. Examples include independent validation of results, meta-analysis, or exploration of novel scientific questions. Requestors must submit a methodologically sound research proposal through the designated access portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No