Clinical trial NCT06976229: Safety and Early Efficacy of iPSC-Derived Motor Neuron Cells (XS228) in Subacute Spinal Cord Injury: A Phase I Trial
Official title: A Phase I Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of Human Allogeneic Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells (XS228 Cell Injection) in Patients With Subacute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Spinal Cord Injury
Safety
Clinical Trials
Efficacy
Induced Pluripotent Stem Cells
Human Motor Neuron Progenitor
Transplantation
Keywords: spinal cord injury
safety
efficacy
clinical trials
Induced Pluripotent Stem Cells
Human motor neuron progenitor
Transplantation
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: XellSmart Biomedical (Suzhou) Company
First posted: 2025-05-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 \<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.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: Day 0 (infusion) → Day 28 (initial safety) → Day 90 (DLT window) → Month 12 (long-term follow-up)
measure: Maximum Tolerated Dose (MTD) Determination
timeFrame: Cohort completes 90-day safety before escalation (total 9-12 months)
Secondary outcomes:
measure: Improvement in ASIA Impairment Scale (AIS) grade
timeFrame: 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.
measure: Changes in American Spinal Injury Association (ASIA) Motor Score
timeFrame: From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.
measure: Changes in American Spinal Injury Association (ASIA) Sensory Score
timeFrame: From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.
measure: Changes in Spinal Cord Independence Measure-III (SCIM-III)
timeFrame: From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Limin Rong, prof and M.D
role: PRINCIPAL_INVESTIGATOR
References: