Clinical Study on the Safety and Efficacy of Human Adipose-Derived Stem Cell Exosomes in the Treatment of Acute Ischemic Stroke
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study employs a double-blind design. The following parties are masked (blinded):
Subjects: Participants will not know whether they are receiving ADSC-exo or placebo (saline).
Investigators and Site Staff: All personnel directly involved in treating subjects, evaluating clinical outcomes (including efficacy scale assessments), and managing subject care during the trial will be blinded to treatment assignment. This includes the Principal Investigator, sub-investigators, and study nurses.
Sponsor's Clinical Team: Personnel from the sponsor involved in the day-to-day monitoring and clinical operations of the trial will remain blinded.
To maintain the blind, the active drug (ADSC-exo solution) and the placebo (saline) are prepared to be identical in appearance, packaging, and labeling. An interactive web response system (IWRS) will manage randomization and drug kit assignment. The sponsor will designate a limited number of unblinded personnel (e.g., an unblinded statistician respon
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years, male or female
- •Patients with acute ischemic stroke within 72 hours of symptom onset
- •Internal carotid artery system stroke
- •For the single-dose study: mild stroke patients (NIHSS score 1-4, inclusive of 1 and 4)
- •For the multiple-dose study: moderate stroke patients (NIHSS score 5-12, inclusive of 5 and 12)
- •Pre-stroke mRS score ≤ 1
- •Subjects or their guardians voluntarily sign the informed consent form
排除标准
- •Moderate or severe stroke (NIHSS score > 12).
- •Lacunar infarction, brainstem or cerebellar infarction (confirmed by DWI-MRI).
- •Requirement for endovascular interventional treatment for the current episode.
- •Intracranial hemorrhagic diseases (including parenchymal, intraventricular, subarachnoid hemorrhage, etc.).
- •Patients with malignant tumors.
- •Patients with severe traumatic brain injury.
- •Patients with primary or secondary immunodeficiency diseases or requiring immunosuppressant medication.
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times the upper limit of normal.
- •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.
- •Presence of severe infection or fever; patients with severe respiratory diseases.
- •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).
- •Patients who are pregnant or lactating at screening, or wish to become pregnant during the study period. Patients allergic to the product
- •Patients allergic to the product or with severe allergic constitution.
- •Patients deemed unsuitable for participation by the investigator, or for whom participation may pose a greater risk.
- •Patients who have participated in another clinical trial within the past 3 months.
- •Patients with prior use of exosomes.
研究组 & 干预措施
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.
干预措施: Human Adipose-Derived Stem Cell Exosomes (Biological)
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.
干预措施: Human Adipose-Derived Stem Cell Exosomes (Biological)
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.
干预措施: Human Adipose-Derived Stem Cell Exosomes (Biological)
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.
干预措施: Human Adipose-Derived Stem Cell Exosomes (Biological)
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.
干预措施: Placebo (Other)
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.
干预措施: Human Adipose-Derived Stem Cell Exosomes (Biological)
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.
干预措施: Placebo (Other)
结局指标
主要结局
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke.
时间窗: 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.
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.
Safety and Tolerability of ADSC-exo Nasal Spray in Acute Ischemic Stroke
时间窗: 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.
Specific Safety Assessments: pulmonary function: Changes in FEV versus baseline
次要结局
- Change in Neurological Function (For Single-Dose Study)(Baseline (Day 1, pre-dose) to Day 14 post-dose.)
- Change in NIHSS Score after 14-Day Treatment (For Multiple-Dose Study)(Baseline (Day 1, pre-dose) to Day 14 (end of treatment).)
- Change in Disability & Daily Function (For Multiple-Dose Study)(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)(Baseline MRI (within screening period, Day -7 to -1) to Day 90 MRI.)
研究者
Yuncheng Wu
Professor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine