Chronic limb threatening ischemia
Conditions
Interventions
Experimental group:Basic treatment + HM2003 injection
Control group:Basic treatment + saline injection
Sponsors
Shanghai Sixth People's Hospital
Eligibility
Sex/Gender
All
Age
20 Years to 80 Years
Inclusion criteria
Inclusion criteria: To be eligible for the trial, all of the following criteria were met: 1. Age >=20 years old and = 4; (4) One or more subpopliteal arteries with stenosis >=70% or occlusion confirmed by DSA within 3 months before randomization; 3. Patients who had undergone previous open surgery or endovascular treatment and had disease recurrence before screening; Or, if the patient is considered by the investigator to be unsuitable for surgery or endovascular treatment after the assessment of new disease; 4. Good organ and bone marrow function, with laboratory findings within 7 days before the first dose meeting the following criteria: (1) hemoglobin >= 90g/L; Platelet count >=100×10^9/L; Neutrophil count >=1.5×10^9/L; (2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 30ml/min/1.73m^2 (calculated using MDRD formula); (4) creatine kinase (CK) <= 2×ULN; (5) glycosylated hemoglobin A1c (HbA1c) <=10.0%; 5. Agree to accept the safety and efficacy evaluation and follow-up as specified in the protocol, and fully understand the content, process and possible adverse reactions of the trial. They were able to complete the study in accordance with the requirements of the trial protocol and had good compliance.
Exclusion criteria
Exclusion criteria: During the screening and examination, if any of the following conditions are met, the patient cannot participate in this clinical trial: 1. Lower limb ischemia meets any of the following conditions: (1) acute lower limb ischemia or acute exacerbation of chronic lower limb ischemia; (2) the area of a single ulcer was more than 10cm^2 or the total number of ulcers was more than 3; (3) ulcers with severe infection (cellulitis, osteomyelitis, etc.) or deep ulcers exposing tendon or bone; (4) gangrene of ischemic limbs (except for local toe gangrene); (5) aorto-iliac artery stenosis of 70% or more; (6) a 20% or greater reduction in ulcer area at randomization or a significant trend toward improvement as judged by the investigator compared with the screening period; (7) The investigator judged that the affected limb was not suitable for multiple intramuscular injections; (8) patients who underwent revascularization (open surgery or endovascular treatment) or sympathectomy or amputation within 4 weeks before signing the informed consent; 2. History of the following diseases or treatments: (1) patients previously diagnosed with proliferative retinopathy or unable to undergo retinopathy examination; (2) patients with a history of malignant tumor or abnormal results of one of the following examinations at the time of screening, which were judged by the investigator to be at risk of cancer: chest X-ray or chest CT examination; Alpha-fetoprotein (AFP); Carcinoembryonic antigen (CEA); Carbohydrate antigen CA19-9 (CA19-9); Carbohydrate antigen CA125 (CA125), restricted to female subjects; Prostate specific antigen (PSA), restricted to male subjects; (3) previous use of gene cell therapy (including plasmid DNA, RNA, genetically modified virus, bacteria or cells, and products based on gene editing technology, etc.) or participation in clinical trials related to gene cell therapy; (4) NYHA functional class III-IV at screening or randomization; (5) previous diagnosis of severe arrhythmia, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate; (6) patients with severe liver disease, such as cirrhosis with jaundice and ascites, at screening or randomization; (7) had a history of major surgery within 3 months before screening or planned to undergo major surgery during the study period; (8) participated in clinical trials of drug interventions other than gene cell therapy products within 3 months before screening (except screening failure), or within 5 half-lives of the drug (whichever is longer); (9) patients with cerebral infarction, cerebral hemorrhage, myocardial infarction or unstable angina pectoris within 3 months before signing the informed consent; (10) Refractory hypertension (systolic blood pressure >=180mmHg or diastolic blood pressure >=110mmHg after adequate antihypertensive treatment); (11) previous history of drug or drug abuse or alcohol abuse; (12) suspected allergic history to the test drug or any component in the test drug; (13) Known infectious diseases such as human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, active hepatitis C virus (HCV) infection, or active tuberculosis that are deemed by the investigator to be ineligible for clinical trial participation: 1) Active HBV infection: At the time of screening, hepatitis B surface antigen (HbsAg) was positive and HBV-DNA viral load was greater than the upper limit of normal reference range of local m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence rate and severity of adverse events (AE), as well as other safety evaluations (including changes from baseline in vital signs, physical examinations, laboratory tests, etc.); | — |
Secondary
| Measure | Time frame |
|---|---|
| The absolute decrease in the average pain score as measured by NRS;The percentage of cases where the average pain score on the NRS decreased by more than 50%;The percentage of cases where rest pain can be completely relieved without the use of painkillers;The time for complete disappearance of resting pain without the use of painkillers;The changes in the affected limb's ABI, TBI, and TcPO2 compared to the baseline values;Change in quality of life score (VascuQol) compared to the baseline;The percentage of complete ulcer healing;The percentage of ulcer area reduction of more than 50%;Based on DSA evaluation of the changes in lower extremity vascular perfusion and new formations compared to the baseline; | — |
Countries
China
Contacts
Public ContactXin Ma/Haiyan Hu
Shanghai Sixth People's Hospital
Outcome results
None listed