A Phase I Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of Human Allogeneic Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells (XS228 Cell Injection) in Patients With Subacute Spinal Cord Injury
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The incidence of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This Phase I clinical trial is designed to evaluate the safety, tolerability of XS228 ( iPSC-Derived Motor Neuron Progenitor Cells) in patients with Subacute Spinal Cord Injury
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 65 years (inclusive), regardless of gender.
- •Etiology: Cervical (C4) to lumbar (L2) spinal cord injury (SCI) caused by traumatic injury or surgery-related factors.
- •Classified as ASIA Impairment Scale (AIS) Grades A, B, or C. MRI-confirmed evidence of spinal cord injury.
- •Disease Stage:
- •Primary SCI occurring 14 to 60 days prior to screening (subacute phase).
- •Contraception:
- •Participants of childbearing potential (male and female) must agree to use effective non-hormonal contraceptive methods during the trial and for 6 months after trial completion.
- •Compliance:
- •Voluntarily participate in the clinical study. Ability to understand and comply with study procedures. Participant or legal guardian can provide written informed consent.
排除标准
- •Neurological Inability
- •Primary spinal cord injury (SCI) during screening with concomitant severe traumatic brain injury precluding neurological function assessment.
- •Respiratory/Circulatory Instability
- •High cervical SCI (C1-C3) causing respiratory/circulatory compromise requiring endotracheal intubation or tracheostomy.
- •Life-Threatening Multiorgan Dysfunction
- •Concurrent severe injuries to other organ systems with life-threatening dysfunction.
- •Unstable Thoracoabdominal Injuries
- •Injuries to lungs, liver, kidneys, spleen, etc., deemed unstable by the investigator.
- •Prior Spinal Pathology
- •History of SCI or coexisting spinal disorders (e.g., ankylosing spondylitis, spinal deformities, primary/metastatic spinal tumors, spinal vascular malformations, syringomyelia).
- •Local Infection/Increased ICP
- •Active infection at the lumbar puncture site or intracranial hypertension during screening.
- •Severe Infections
- •Sepsis, septic shock, or severe pneumonia (per IDSA/ATS 2007 diagnostic criteria).
- •Confounding Neurological/Psychiatric Conditions
- •Parkinson's disease, severe dementia, myasthenia gravis, stroke, Guillain-Barré syndrome, diabetic neuropathy, or other conditions interfering with study assessments.
- •Cardiac Abnormalities (any of the following):
- •Congestive heart failure (NYHA Class III/IV). Severe uncontrolled arrhythmias (e.g., sick sinus syndrome, third-degree AV block).
- •Unstable angina or acute myocardial infarction within 3 months prior. Pulmonary Complications
- •Pulmonary hypertension, pulmonary embolism, or suspected embolism during screening.
- •Uncontrolled Hypertension/Hypotension
- •Systolic BP >160 mmHg or diastolic BP >100 mmHg; or systolic BP <90 mmHg or diastolic BP <60 mmHg.
- •Active Autoimmune Diseases
- •Requiring immunosuppressants (e.g., uncontrolled hyperthyroidism, systemic lupus erythematosus).
- •Immunosuppressant Non-Compliance
- •Unwillingness or inability to use immunosuppressants per protocol.
- •Laboratory Abnormalities (any of the following):
- •ALT/AST >2×ULN or total bilirubin >2×ULN. eGFR <60 mL/min/1.73m² (CKD-EPI 2021 formula). APTT/PT >2.5×ULN (without anticoagulants). Platelets <100×10⁹/L or hemoglobin <90 g/L. Allergy
- •History of severe allergies or hypersensitivity to trial drug/excipients (human albumin, lactated Ringer's solution).
- •Infectious Diseases
- •HBsAg+ with HBV DNA >1000 IU/mL; HCV-Ab+; HIV-Ab+; or TP-Ab+. Lumbar Puncture Refusal
- •Unwillingness to undergo intrathecal administration procedures. Pregnancy/Lactation
- •Females who are pregnant or breastfeeding. Malignancy
- •Active malignancy or anticancer therapy within 5 years prior. Recent Clinical Trial Participation
- •Enrollment in another drug trial within 3 months prior. Investigator Discretion
- •Any condition deemed unsuitable for participation by the investigator.
研究组 & 干预措施
XS228 for injection
The Single Ascending Dose (SAD) and Muliple Ascending Dose (MAD) stages were built up in the study. XS228 in SAD and MAD following intrathecal injection through lumbar puncture in Subacute Spinal Cord Injury participants.
干预措施: Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells (Biological)
结局指标
主要结局
The incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 28 days after administration in the SAD treatment and 28 days after the final (fourth) administration in the MAD treatment
To evaluate the safety and tolerability of XS228 in A single dose and the last dose of MAD treatment of Subacute Spinal Cord Injury through Adverse events (AE) related to XS228 ,incidence of SAE（serious adverse events).The severity of AEs observed during the trial will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
DLT（Dose-limiting toxicity）
时间窗: 28 days after administration in the SAD treatment and 28 days after the final (fourth) administration in the MAD treatment
To evaluate the safety and tolerability of XS228 in A single dose and the last dose of MAD treatment of Subacute Spinal Cord Injury through DLT（Dose-limiting toxicity）.A DLT is defined as any Grade 3 or higher adverse event (based on NCI-CTCAE Version 5.0) that occurs within 28 days following single-dose administration in the SAD treatment or the final dose in the MAD treatment ， which is assessed as related to XS228, or any other significant adverse event as determined by the Safety Review Committee (SRC) .
RP2D（Recommended Phase 2 Dose）
时间窗: After the last participant in the MAD treatment of the Phase I trial completes the 28-day DLT observation period
After the last participant in the MAD treatment of the Phase I trial completes the 28-day DLT observation period following their final dose, the Safety Review Committee (SRC) and the sponsor will jointly determine the recommended dose for Phase II based on safety and preliminary efficacy data from Phase I.
次要结局
- Improvement in ASIA Impairment Scale (AIS) grade(Improvement in ASIA Impairment Scale (AIS) grade from baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.)
- Changes in American Spinal Injury Association (ASIA) Motor Score(From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.)
- Changes in American Spinal Injury Association (ASIA) Sensory Score(From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.)
- Changes in Spinal Cord Independence Measure-III (SCIM-III)(From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.)