Safety and Early Efficacy of iPSC-Derived Motor Neuron Progenitor Cells (XS228) in Subacute Spinal Cord Injury: A Phase I Trial

NCT06976229 | Recruiting Phase 1 DMC

• 1 other identifier: XS228-Allo-SCI-CN1-P01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I clinical trial is designed to evaluate the safety, tolerability of XS228 ( iPSC-Derived Motor Neuron Progenitor Cells) in patients with Subacute Spinal Cord Injury

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

Outcome Measures

Primary Outcomes (3)

• The incidence of adverse events (AEs) and serious adverse events (SAEs)

  To evaluate the safety and tolerability of XS228 in A single dose and the last dose of MAD treatment of Subacute Spinal Cord Injury through Adverse events (AE) related to XS228 ,incidence of SAE（serious adverse events).The severity of AEs observed during the trial will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

  28 days after administration in the SAD treatment and 28 days after the final (fourth) administration in the MAD treatment

• DLT（Dose-limiting toxicity）

  To evaluate the safety and tolerability of XS228 in A single dose and the last dose of MAD treatment of Subacute Spinal Cord Injury through DLT（Dose-limiting toxicity）.A DLT is defined as any Grade 3 or higher adverse event (based on NCI-CTCAE Version 5.0) that occurs within 28 days following single-dose administration in the SAD treatment or the final dose in the MAD treatment ， which is assessed as related to XS228, or any other significant adverse event as determined by the Safety Review Committee (SRC) .

  28 days after administration in the SAD treatment and 28 days after the final (fourth) administration in the MAD treatment

• RP2D（Recommended Phase 2 Dose）

  After the last participant in the MAD treatment of the Phase I trial completes the 28-day DLT observation period following their final dose, the Safety Review Committee (SRC) and the sponsor will jointly determine the recommended dose for Phase II based on safety and preliminary efficacy data from Phase I.

  After the last participant in the MAD treatment of the Phase I trial completes the 28-day DLT observation period

Secondary Outcomes (4)

• 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 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 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.

Study Arms (1)

XS228 for injection

EXPERIMENTAL

The Single Ascending Dose (SAD) and Muliple Ascending Dose (MAD) stages were built up in the study. XS228 in SAD and MAD following intrathecal injection through lumbar puncture in Subacute Spinal Cord Injury participants.

Biological: Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells

Interventions

Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells BIOLOGICAL

Description: The Single Ascending Dose (SAD) and Muliple Ascending Dose (MAD) stages were built up in the study. XS228 in SAD and MAD following intrathecal injection through lumbar puncture in subacute spinal cord Injury participants.For SAD,the participants will single intrathecal injection with the dose level as 5×10\^7 cells 、1.5×10\^8 cells. For MAD, the participants will intrathecal injection of XS228 in Day 1, Day15, Day 29, Day 43 under the dose level of 5×10\^7 cells、1.5×10\^8 cells.Dose escalation followed a rule-based 3+3 design. XS228 is an investigational, allogeneic cell therapy product composed of motor neuron progenitor cells (MNPCs) derived from human induced pluripotent stem cells (iPSCs). This advanced therapy medicinal product (ATMP) is being developed for the treatment of subacute spinal cord injury and represents a novel approach in regenerative medicine.

Also known as: XS228 Cell Injection, XS228

XS228 for injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• XellSmart Bio-Pharmaceutical (Suzhou) Co., Ltd.: lead
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (1)

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Limin Rong, prof and M.D

  Third Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael LEE

CONTACT

+86 21 64027719; CEO@xellsmart.com

Mao Pang, prof and M.D

CONTACT

+86-020-85252015; pangmao6@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 16, 2025
• Study Start: July 2, 2025
• Primary Completion (Estimated): February 21, 2028
• Study Completion (Estimated): May 30, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-08

Locations

CN (1)