Human Placenta-derived 3D Mesenchymal Stem Cells(Guojianqingke)

A Phase I/IIa Clinical Trial on the Safety, Tolerability, and Preliminary Efficacy of Human Placental-Derived 3D Mesenchymal Stem Cell Injection Administered Via the Intravenous Route in Patients With Acute Ischemic Stroke (AIS): A Randomized, Double-Blind, Placebo-Controlled Study

This is a Phase I/IIa clinical trial evaluating human placental-derived 3D mesenchymal stem cell (MSC) injection in patients with acute ischemic stroke (AIS). Phase I is a single-dose escalation study to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Phase IIa explores preliminary efficacy. Each participant undergoes screening (up to 72 hours before treatment), a single-day treatment period, and follow-up for up to 720 days (24 months).

This study consists of two sequential phases:

Phase I (Dose Escalation): A single ascending dose design to evaluate safety and tolerability of intravenous human placental-derived 3D MSC injection in AIS patients, and to establish the MTD and RP2D.

Phase IIa (Expansion): A randomized, double-blind, placebo-controlled evaluation of preliminary efficacy at the RP2D.

Study Duration: Screening within 72 hours of stroke onset; single-day treatment; follow-up visits through Day 720.

Inclusion Criteria:

1. Age ≥18 years and ≤80 years; any gender
2. Body weight 45-90 kg
3. Diagnosed with acute ischemic stroke, with onset between 6 and 72 hours (inclusive) prior to enrollment; received thrombolysis or not planned for thrombolysis and no planned thrombectomy
4. NIHSS score 6-20, with NIHSS item 1a (Level of Consciousness) <2
5. Participant or legally authorized representative able to understand and provide written informed consent

Exclusion Criteria:

1. Significant pre-stroke disability (pre-stroke modified Rankin Scale [mRS] score ≥2)；

2. History of intracerebral hemorrhage, subarachnoid hemorrhage, or hemorrhagic transformation after this ischemic stroke (imaging re-evaluation before planned dosing shows new bleeding within the infarct area accompanied by neurological deterioration [e.g., NIHSS total score increased ≥4 points from admission], judged by the investigator as unsuitable for clinical trial participation); or presence of cerebrovascular malformation, multiple sclerosis, severe traumatic brain injury history, encephalitis, or other conditions causing stroke-like symptoms

3. Uncontrolled systemic diseases, including but not limited to: hypertension (systolic BP >180 mmHg and/or diastolic BP ≥120 mmHg), diabetes (diabetic acute complications such as ketoacidosis, hyperosmolar hyperglycemic state, lactic acidosis, or hypoglycemic coma within 3 months, or difficult-to-control diabetes [blood glucose >16.8 mmol/L or <2.8 mmol/L]), renal disease (eGFR <30 mL/min/1.73m²), hepatic failure (Child-Pugh Class C), severe heart failure (NYHA Class IV), severe chronic respiratory disease

4. History of seizure (except secondary epilepsy not currently requiring drug treatment)

5. History of brain tumor or malignancy within the past 5 years, including concurrent second primary malignancy, except: a) radically excised non-melanoma skin cancer; b) radically treated cervical carcinoma in situ; c) radically treated papillary thyroid carcinoma; d) radically treated localized prostate cancer; e) radically treated ductal carcinoma in situ of the breast

6. History of any of the following:

   1. Active or uncontrolled autoimmune disease (e.g., antiphospholipid antibody syndrome)
   2. Protein C or protein S deficiency
   3. Sickle cell anemia
   4. Deep vein thrombosis
   5. Pulmonary embolism
   6. Cerebrovascular malformation (e.g., moyamoya disease)

7. Any concomitant disease or physical condition (e.g., severe arthritis, amputation, blindness, severe disability from prior stroke) that, in the investigator's judgment, would significantly interfere with accurate assessment of mRS, NIHSS, or BI scores

8. Major surgery within the past 30 days (e.g., thoracotomy, cardiac surgery, abdominal surgery, intracranial surgery)

9. Currently severe illness, including:

   1. Severe heart failure (NYHA Class III-IV)
   2. Severe febrile illness (any fever within 14 days before dosing requiring systemic anti-infective treatment)
   3. Primary or secondary immunodeficiency disease, or long-term or recent high-dose immunosuppressant or systemic corticosteroid therapy before screening
   4. Hemorrhagic disorder or bone marrow transplantation
   5. Any comorbidity that the investigator believes may shorten survival or limit ability to complete the study
   6. Uncontrolled depression affecting daily life before stroke, dementia that may affect clinical assessment, or other neurological or psychiatric disorders that the investigator believes may affect study assessment

10. Uncontrolled active infection; or systemic anti-infective treatment within 7 days before dosing that the investigator assesses may shortly convert to uncontrolled active infection

11. Organ function meeting any of the following:

    Hematology:

    Absolute neutrophil count (ANC) <1.0×10⁹/L Platelets (PLT) <75×10⁹/L Hemoglobin (Hb) <80 g/L

    Hepatic/Renal Function:

    Alanine aminotransferase (ALT) >2.5×ULN Aspartate aminotransferase (AST) >2.5×ULN Total bilirubin (TBIL) >1.5×ULN Creatinine >1.5×ULN

    Coagulation:

    Phase I: Not receiving anticoagulant or antithrombotic therapy: PT and APTT >1.25×ULN, INR >1.4; Receiving anticoagulant or antithrombotic therapy: PT and APTT >1.5×ULN, INR >3.0 Phase IIa: Not receiving anticoagulant therapy: APTT >2.0×ULN or PT >2.0×ULN; Receiving anticoagulant therapy: judged by investigator to have severe bleeding risk

12. Clinically significant uncorrected electrolyte disturbances (e.g., hyperkalemia, hypernatremia) that the investigator believes may affect study assessment

13. Unable to undergo head CT/MRI for any reason (e.g., cardiac pacemaker, metal implants, claustrophobia)

14. History of drug abuse or alcohol abuse within the past year

15. Allergy to bovine or porcine products, human serum albumin products, or known allergy to gentamicin

16. Participation in another investigational drug, device study, or stem cell/immune cell therapy within 3 months before treatment

17. History of blood transfusion or vaccination with attenuated/live vaccine within 3 months before screening

18. Pregnant or lactating women; or participants with pregnancy plans during the study period, or unwilling to use effective contraception; or females of childbearing potential with positive pregnancy test; or female participants on long-term oral contraceptives (continuous use >30 days)

19. Other reasons deemed by the investigator as unsuitable for participation or inability to complete study procedures (e.g., lack of willingness)