safety and early efficacy of ipsc-derived motor neuron cells (xs228) in subacute spinal cord injury: a phase i trial

Conditions: Spinal Cord Injury; Safety; Clinical Trials; Efficacy; Induced Pluripotent Stem Cells; Human Motor Neuron Progenitor; Transplantation

Summary: the goal of this clinical trial is to evaluate the safety, tolerability, and preliminary efficacy of ipsc-derived motor neuron progenitor cells (imnp) in the treatment of spinal cord injury (sci) in adult participants (age and sex criteria as per inclusion/exclusion criteria). the main questions it aims to answer are: primary safety \& tolerability (phase i): what is the maximum tolerated dose (mtd) and dose-limiting toxicity (dlt) profile of imnp transplantation in sci patients? participants will: undergo screening assessments (mri/dti, electrophysiological tests, lab work) to confirm eligibility. receive intraspinal transplantation of imnp cells at the assigned dose (phase i: dose-escalation). complete long-term follow-up (up to 1 year) with repeated neurological exams, imaging, and safety monitoring (e.g., ae/sae tracking, lab tests). adhere to rehabilitation protocols and report concurrent therapies.


Eligibility criteria:
inclusion criteria: 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. severity: 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. exclusion criteria: * 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 \ 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.

Keywords: spinal cord injury safety efficacy clinical trials induced pluripotent stem cells human motor neuron progenitor transplantation