Safety and Early Efficacy of iPSC-Derived Motor Neuron Progenitor Cells (XS228) in Subacute Spinal Cord Injury: A Phase I Trial

Exclusion Criteria36

• 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.