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

NCT06974968 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: XS228-Allo-SCI-CN2-P01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Cord Injury; Safety; Efficacy; Clinical Trial; Induced Pluripotent Stem Cells; Human Motor Neuron Progenitor; Transplantation; RCT

Keywords

Spinal Cord Injury; Safety; efficacy; clinical trial; Induced Pluripotent Stem Cells; Human motor neuron progenitor; Transplantation; RCT

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (4)

• 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.

• Safety and Tolerability

  From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.

Study Arms (2)

XS228 Interventional Group

ACTIVE COMPARATOR

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, Day 43).

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

Placebo Control Group

PLACEBO COMPARATOR

Standard rehabilitation protocols

Other: Placebo

Interventions

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

Description: XS228 Cell Injection 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 spinal cord injury (SCI) and represents a novel approach in regenerative medicine.

XS228 Interventional Group

Placebo OTHER

Standard rehabilitation protocols

Also known as: Standard rehabilitation protocols

Placebo Control Group

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

Location

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Phase II study adopts a randomized, double-blind, placebo-controlled design. Investigators and participants remain blinded to treatment allocation. All investigational products and placebos will be identically packaged to maintain blinding for participants, investigators (physicians and coordinators), and monitors. Treatment assignments will remain confidential until database lock and prior to statistical analysis, except in cases of medical emergencies. Due to the need for cell-based product preparation based on randomization results, an unblinded team will be established to handle drug preparation and packaging. Unblinded team members will not perform any clinical assessments. Further details are provided in the Drug Management Manual.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 16, 2025
• Study Start (Estimated): May 25, 2028
• Primary Completion (Estimated): May 25, 2031
• Study Completion (Estimated): May 26, 2031
• Last Updated: November 25, 2025

Record last verified: 2025-08

Locations

CN (1)