Efficacy of iPSC-Derived Motor Neuron Cells (XS228) in Subacute Spinal Cord Injury: A Phase II Randomized Controlled Trial

Title: A Randomized, Double-Blind, Placebo-Controlled Phase II Trial to Evaluate the Efficacy and Safety of XS228 Cell Injection in Patients with Subacute Thoracic or Lumbar SCI

Study Type: Interventional (Clinical Trial) Phase: Phase II Allocation: Randomized (2:1, XS228 vs. Placebo) Masking: Double-blind (Participant, Investigator) Primary Purpose: Treatment

Hypothesis:

XS228 (allogeneic iPSC-derived motor neuron progenitor cells) will demonstrate statistically significant improvement in motor function (ASIA Motor Score) compared to placebo at 6 months post-treatment.

The therapy will exhibit an acceptable safety profile with no dose-limiting toxicities (DLTs).

Intervention Details

Investigational Product:

XS228 Cell Injection: Cryopreserved suspension of optimal dose from Phase I. Placebo: Normal saline with identical packaging/labeling. Administration: 4 intrathecal injection via lumbar puncture (Day 1, Day 15, Day 29 and Day 43).

Concomitant Therapies:

Standard rehabilitation protocols (uniform across sites). Prohibited: Other experimental therapies or stem cell treatments during the study.

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 <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