patients with critical limb ischemia
Conditions
Interventions
Cohort Two (Ulcer) - Low-dose Group:Three doses (at low doses) will be administered on D1, D15 and D29.
Cohort Two (Ulcer) - Medium-dose group:Three doses (medium doses) will be administered on D1, D15 and D29.
Queue One (Rest Pain) - Low-dose group:Three doses (at low doses) will be administered on D1, D15 and D29.
Queue One (Rest Pain) - Medium-dose group:Three doses (medium doses) will be administered on D1, D15 and D29.
Queue One (Rest Pain) - High-dose group:Three doses (high doses) will be administered on D1, D15 and D29.
Cohort One (Rest pain) - Placebo group:Three doses (placebo) will be administered on D1, D15 and D29.
Cohort Two (Ulcer) - High-dose group:Three doses (high doses) will be administered on D1, D15 and D29.
Cohort Two (Ulcer) - Placebo group:Three doses (placebo) will be administered on D1, D15 and D29.
Sponsors
Zhongshan Hospital Affiliated to Fudan University
Eligibility
Sex/Gender
All
Age
20 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Age >=20 years old and =70%) or occlusion of superficial femoral artery or popliteal artery or subknee artery was confirmed by DSA or CTA within 3 months before randomization; 3. Before randomization, the area of a single ulcer on the study limb was = 80 g/L; (2) Platelet >=75×109/L; (3) Neutrophil count >=1.5×109/L; (4) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <=3×ULN, total bilirubin <=1.5×ULN; (5) Serum creatinine (Cr) <=2×ULN; (6) Hemoglobin A1c (HbA1c) <=12.0% (within 28 days before the first dose); 6. Those who understand the research procedures and methods, voluntarily participate in this experiment, and sign the informed consent letter in person.
Exclusion criteria
Exclusion criteria: 1. The study of lower limb ischemia meets any of the following conditions: (1) acute lower limb ischemia or acute exacerbation of chronic lower limb ischemia; (2) Ulcers with severe infection (cellulitis, osteomyelitis, etc.) or deep ulcers exposing the tendon or bone; (3) gangrene occurs (except local gangrene of the toes); (4) 70% or more main-iliac artery stenosis; (5) The investigator judged that the study limb was not suitable for receiving multiple intramuscular injections; (6) Revascularization surgery or sympathectomy or major amputation (amputation above ankle) within 4 weeks before signing the informed consent; 2. Have the following medical conditions or treatment history: (1) proliferative diabetic retinopathy or other proliferative retinopathy, or those who cannot be tested for retinopathy; (2) There is a history of malignant tumor, or abnormal results of any of the following tests during screening, and the researcher determines that there is a tumor risk: (a) Chest X-ray or chest CT examination; (b) alpha-fetoprotein (AFP); (c) Carcinoembryonic antigen (CEA); (d) carbohydrate antigen CA19-9 (CA19-9); (e) Carbohydrate antigen CA125 (CA125), limited to female subjects; (f) Prostate-specific antigen (PSA) for male subjects only; (g) Cervical smear test, female subjects only; (h) Mammography/ultrasound, female only; (3) have previously used gene cell therapy (including plasmid DNA, RNA, genetically modified viruses, bacteria or cells, and products based on gene editing technology, etc.) or participated in clinical trials related to gene cell therapy (except those who revealed the use of placebo); (4) Participated in clinical trials of other drug interventions other than gene cell therapy products within 3 months prior to signing the informed consent (except for screening losers), or the screening trend is within 5 half-lives of the drug (whichever is longer); (5) Levels III-IV of heart function as defined by the New York Heart Association (NYHA) (see Annex 2 for grading standards); (6) Severe liver diseases, such as decompensated cirrhosis with jaundice and ascites; (7) Patients who received surgery before signing the informed consent and are still in the postoperative risk period, and are not suitable to participate in clinical trials according to the researchers; (8) Patients with cerebral infarction (except lacunar cerebral infarction), cerebral hemorrhage, myocardial infarction, and unstable angina pectoris within 3 months before signing the informed consent; (9) Refractory hypertension (systolic blood pressure =180mmHg or diastolic blood pressure =110mmHg after adequate antihypertensive treatment); (10) A history of drug use or drug abuse or alcohol abuse; (11) Suspected allergic history to the experimental drug or any component of the experimental drug; (12) Infectious diseases such as known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, active hepatitis C virus (HCV) infection, or active tuberculosis that have been determined by the investigator to be unsuitable for clinical trials: (a) Active HBV infection: Hepatitis B surface antigen (HbsAg) positive at the time of screening and HBV-DNA viral load greater than the upper limit of the normal reference range in local healthcare facilities; (b) Active HCV infection: Both HCV antibody test results and HCV-RNA test results were positive at screening. (13) Positive pregnancy test; 3. General situation: (1) Can not correctly describe sy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change value of the pain score in Cohort one compared with the baseline;The change value of ulcer area in Cohort two compared with the baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| The complete disappearance rate of pain at each visit in Cohort one;Time for complete disappearance of pain in Cohort one;The time from the administration of the first dose to the complete disappearance of pain in the study limb in Cohort One;The proportion of subjects whose pain scores at each visit decreased by = 50% compared with the baseline;The change values of pain scores at each visit (except for D 90 and D 180) from the baseline;The complete healing rate of ulcers at each visit in Cohort Two;The complete healing rate of ulcers in Cohort two;The time from the administration of the drug for the first dose to the complete healing of the ulcer on the studied limb;The proportion of subjects whose ulcer area at each visit decreased by = 50% compared with the baseline;The change values of ulcer area at each visit (except D90 and D180) in Cohort Two compared with the baseline;The complete disappearance rate of pain at each visit in Cohort Two;The time when pain completely disappears in Cohort Two;The time from the administration of the drug for the first dose in Cohort Two to the complete disappearance of pain in the study limb;;The changes of ankle-brachial index (ABI) at each visit compared with the baseline;The proportion of subjects undergoing D180 vascular reconstruction (open surgery or endovascular treatment);The major amputation rate and mortality rate of patients on D180;Safety;Pharmacokinetics and immunogenicity; | — |
Countries
China
Contacts
Public ContactWeiguo Fu
Zhongshan Hospital Affiliated to Fudan University
Outcome results
None listed