Safety and Early Efficacy of iPSC-Derived Motor Neuron Cells (XS228) in Subacute Spinal Cord Injury: A Phase I Trial
- Conditions
- Spinal Cord InjurySafetyClinical TrialsEfficacyInduced Pluripotent Stem CellsHuman Motor Neuron ProgenitorTransplantation
- Interventions
- Biological: Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells
- Registration Number
- NCT06976229
- Lead Sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 12
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase I: MAD (Multiple Ascending Dose ) and MTD (Maximum tolerated dose)Group Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells 5×10\^7 cells/patient, 1.5×10\^8 cells/patient. Dose escalation followed a rule-based 3 + 3 design
- Primary Outcome Measures
Name Time Method Safety and Tolerability Day 0 (infusion) → Day 28 (initial safety) → Day 90 (DLT window) → Month 12 (long-term follow-up) Description: Systematic evaluation of:
Acute/subacute adverse events (AEs) up to 28 days post-infusion Dose-limiting toxicities (DLTs) within the first 90 days Immunogenicity (anti-HLA antibodies, T-cell responses)
Assessment Methods:
CTCAE v5.0 grading Neurological monitoring (ISNCSCI exams) CSF analysis for inflammation markersMaximum Tolerated Dose (MTD) Determination Cohort completes 90-day safety before escalation (total 9-12 months) Description: Dose-escalation study (3+3 design) across 3 cohorts:
Cohort 1: 0.5 × 10⁶ cells/kg Cohort 2: 1.0 × 10⁶ cells/kg (target therapeutic dose) Cohort 3: 2.0 × 10⁶ cells/kg (optional) Stopping Criteria: ≥33% DLT rate in any cohort
- Secondary Outcome Measures
Name Time Method 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 motor scores assessed by the ASIA score scale (total score range from 0 to 100, higher values represent a better outcome)
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 sensory scores assessed by the ASIA score scale (total score range from 0 to 224, higher values represent a better outcome)
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. SCIM-III(range: 0-100, with lower score indicating greater disability)
Trial Locations
- Locations (1)
The Third Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The Third Affiliated Hospital of Sun Yat-sen University🇨🇳Guangzhou, Guangdong, ChinaLimin Rong, prof and M.DContact02085253333ronglm@mail.sysu.edu.cn