GD-11 for Injection in the Treatment of Acute Ischemic Stroke

Phase III Clinical Trial of GD-11 for Injection in the Treatment of Acute Ischemic Stroke - A Multi-Center, Randomized, Double-Blind, Parallel, Placebo-Controlled Phase III Clinical Study with the primary objective of evaluation of the efficacy and safety of GD-11 for injection in the treatment of acute ischemic stroke patients within 48 hours. The subject has a clinical diagnosis of acute ischemic stroke, within 48 hours from stroke onset to start of study treatment, with a National Institutes of Health Stroke Scale (NIHSS) between 6 and 20, had a total score of upper and lower limbs on motor deficits ≥ 2. The primary outcome is the proportion of subjects with mRS score ≤ 1 at 90 days after treatment.

A multicenter, randomized, double-blind, parallel, placebo-controlled trial design was used. Subjects were randomly assigned in a 1:1 ratio to the experimental group (GD-11 for injection treatment group) and the control group (GD-11 for injection placebo group). Randomization stratification factors included onset time (≤24 hours, \>24 hours) and center.Continuous treatment was performed for 10 days (20 times), followed up to 90 days after the first administration.

The trial was divided into three phases: screening/baseline phase, treatment phase, and follow-up phase.

Screening/baseline phase: Subjects entered the screening/baseline phase after signing the informed consent for screening examinations.

Treatment phase: Eligible subjects were randomly assigned in a 1:1 ratio to receive GD-11 for injection or placebo for injection for 10 days (20 times). During the treatment, protocol-required examinations were performed and safety was evaluated.

Follow-up phase: Subjects who completed the treatment entered the follow-up phase and were followed up to 90 days after the first administration.

Stroke-related scale scores were performed on the 10th, 30th, and 90th days after the first use of the test drug. Adverse events were recorded during the treatment and follow-up phases to further evaluate safety.

Eligibility Criteria:
Inclusion Criteria:

Only those who meet all of the following items will be enrolled:

1. age ≥18 years and \<81 years, male or female;
2. National Institutes of Health Stroke Scale (NIHSS) score: 6 ≤ NIHSS ≤ 20, and the sum of item 5 Upper Extremity and item 6 Lower Extremity scores ≥ 2 after the onset of this event;
3. The onset of the disease is within 48 hours (including 48 hours);
4. Patients who are diagnosed with ischemic stroke according to the requirements of the latest guidelines such as "Diagnostic Points of Various Major Cerebrovascular Diseases in China 2019" or "Clinical Management Guidelines of Cerebrovascular Diseases in China (2nd edition)", and who have a good healing after the first onset or the last onset (mRS score ≤1 before this onset);
5. Obtaining informed consent approved by the Ethics Committee voluntarily signed by the patients or their legal representatives.

Exclusion Criteria:

Those who met one of the following items at screening will not be eligible for enrollment:

1. intracranial hemorrhagic disease as seen on cranial imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.; if blood seepage only, the suitability for enrollment may be based on the investigator's judgment;
2. severe impairment of consciousness: item score \>1 on the 1a level of consciousness of the NIHSS;
3. thrombolysis, thrombolysis or intervention has been applied or is planned to be applied after this episode;
4. transient ischemic attack (TIA);
5. the patient's blood pressure remains ≥ 220 mmHg systolic or ≥ 120 mmHg diastolic after control;
6. patients with a previous diagnosis of severe mental disorders as well as patients with dementia;
7. patients who have been diagnosed with severe active liver disease, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc.; or ALT (Alanine amino Transferase) or AST (Aspartate amino Transferase) \> 2.0 x ULN (Upper Limit of Normal Value);
8. patients who have been diagnosed with severe active renal disease, renal insufficiency; or serum creatinine \> 1.5 × ULN;
9. after the onset of the disease, the drug with neuroprotective effect has been used in the marketing, such as commercially available edaravone, edaravone dextran edaravone/(+)-2-Decanol injection concentrated solution, nimodipine, gangliosides, cytidine diphosphate, piracetam, oxiracetam, butylphenyl peptide, human urinary kallidinogenase (Urinary Kallidinogenase), cinepazide, murine nerve growth factor, cerebral vivax (hydrolysate of cerebral proteins), calf's blood deprivation of protein injection, calf's blood deprivation of protein extract injection and so on.
10. previously diagnosed with concurrent malignant tumors and undergoing anti-tumor therapy; for subjects diagnosed with malignant tumors after enrollment, continued participation in the study may be based on the investigator's judgment and the subject's wishes;
11. previously diagnosed with a serious systemic disease with an expected survival of \<90 days;
12. the patient is pregnant, breastfeeding and the patient/patient's partner has the potential for pregnancy and plans to become pregnant during the trial period
13. patients with a previously known hypersensitivity to GD-11 for Injection and its excipients;
14. history of major surgery within 4 weeks prior to enrollment that in the investigator's assessment affects neurologic function scores or affects 90-day survival;
15. participation in another clinical study within 30 days prior to randomization or ongoing participation in another clinical study; Not considered by the investigator to be suitable for participation in this clinical study.