Efficacy of iPSC-Derived Motor Neuron Cells (XS228) in Subacute Spinal Cord Injury: A Phase II Randomized Controlled Trial
Status and phase
Conditions
Treatments
Details and patient eligibility
About
Purpose: This clinical trial is studying an investigational cell therapy called XS228-a lab-made stem cell product designed to help repair damaged nerves in the spinal cord. The goal is to see if XS228 is safe and can improve movement, sensation, and function in people with recent spinal cord injuries.
Study Treatment: XS228 contains specialized nerve-supporting cells derived from human stem cells. These cells are injected into the spinal fluid (intrathecal administration) in a single dose.
Who Can Join? Adults aged 18-65 with a spinal cord injury (thoracic or lumbar level) that occurred 2-12 weeks before enrollment. Participants must have severe but incomplete paralysis (ASIA Impairment Scale Grade A , B or C).
Study Plan:
Phase II (Main Study): About 60 participants will be randomly assigned to receive either XS228 or a placebo (inactive solution) in a 2:1 ratio.
Follow-up: Patients will be monitored for 1 year, with regular check-ups to assess safety, nerve function, and recovery progress.
What Researchers Are Looking For:
Primary Goal: Measure changes in leg and arm function using the ASIA Motor Score at 6 months.
Secondary Goals:
Improvement in ASIA Impairment Scale (AIS) grade (e.g., from "complete" to "incomplete" paralysis).
Recovery of sensation and bladder/bowel control. Safety (monitoring for side effects like infections or immune reactions). Exploratory Tests: MRI scans and biomarker tests in spinal fluid to see if the treatment helps nerve regrowth.
Why This Study Matters: If successful, XS228 could become the first stem cell therapy to promote meaningful recovery in spinal cord injury patients. Currently, no treatments exist to repair nerve damage-this trial aims to change that.
Full description
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 0, Day 14, Day 28 and Day 42).
Concomitant Therapies:
Standard rehabilitation protocols (uniform across sites). Prohibited: Other experimental therapies or stem cell treatments during the study.
Enrollment
Sex
Ages
Volunteers
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
Trial design
Primary purpose
Allocation
Interventional model
Masking
60 participants in 2 patient groups, including a placebo group
Trial contacts and locations
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Central trial contact
Mao Pang, prof and M.D; Limin Rong, prof and M.D
Data sourced from clinicaltrials.gov
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