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

Официальное название

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

Обзор

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

Вмешательства

• Биопрепарат Allogeneic Human Induced Pluripotent Stem Cell (iPSC)-Derived Motor Neuron Progenitor Cells
  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.Dos

Первичные конечные точки

• The incidence of adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: 28 days after administration in the SAD treatment and 28 days after the final (fourth) administration in the MAD treatment]
• DLT（Dose-limiting toxicity） [Срок оценки: 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） [Срок оценки: After the last participant in the MAD treatment of the Phase I trial completes the 28-day DLT observation period]

Вторичные конечные точки (4)

• Improvement in ASIA Impairment Scale (AIS) grade [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: From baseline at Day 29, Day 90, Day 180, Day 270, and Day 360 after the first dose administration.]

Критерии участия

Критерии включения

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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Third Affiliated Hospital of Sun Yat-sen University — Гуанчжоу

Публикации

• Pang M, Kang J, Yang Y, He T, Yao S, Hu B, Li X, Liu B, Rong L. Safety and early efficacy of iPSC-derived motor neuron progenitor cells in subacute spinal cord injury: protocol for a phase I, multicentre, open-label, single-arm trial. BMJ Open. 2026 Jul 8;16(7):e111718. doi: 10.1136/bmjopen-2025-111718. PMID 42419896

Идентификаторы

NCT: NCT06976229 · XS228-Allo-SCI-CN1-P01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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