patients with critical limb ischemia
Conditions
Interventions
Single dose increase-investigate drug:Single-dose investigate drug, 16 µg-128 µg
Single dose increase-placebo:Single-dose placebo, 16 µg-128 µg
Multiple dosing increases-investigate drug:Multiple dose investigate drug,16µg-128µg
Multiple dosing increases-placebo:Multiple dose placebo, 16 µg-128 µg
Sponsors
Zhongshan Hospital Affiliated to Fudan University
Eligibility
Sex/Gender
All
Age
20 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, between 20 and 80years of age. 2. According to digital subtraction angiography (DSA) or computed tomographic arteriography (CTA), patients diagnosed with lower limb arterial ischemic disease with Rutherford grade 4 (with rest pain) or grade 5 (with ulcer) based on the medical history and clinical manifestations. (if both limbs of the subject suffer from lower limb arterial ischemic disease, it is up to the investigator to select one limb for the study). 1) Ankle systolic pressure=70%) or occlusion of superficial femoral artery or popliteal artery or inferior knee artery. 3. Ischemic rest pain or ulcer of the lower limb recurred after open surgery or intravascular treatment, or the investigators judged that open surgery or intravascular treatment was not appropriate. 4. Adequate organ and bone marrow function. 1) Hemoglobin >= 90 g/L; 2) Platelet count >= 100 × 10^9/L; 3) Neutrophil count >=1.5×10^9/L; 4) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 30 ml/min/1.73 m^2 (calculated using the MDRD formula, Annex 2); 6) Creatine kinase (CK) <= 2 x ULN; 7) Glycosylated hemoglobin A1c (HbA1c) <= 10.0%; 5. Patients can understand the procedures and methods of this trial and sign informed consent.
Exclusion criteria
Exclusion criteria: 1. Lower limb ischemia meets any of the following criteria: 1) Patients with acute lower limb ischemia or acute exacerbation of chronic lower limb ischemia. 2) Lower limb ulcer with severe infection (cellulitis, osteomyelitis, etc.), distal fascia or bone exposure were observed. 3) Gangrene in ischemic lower limb was observed. 4) Main-iliac artery stenosis >=70%. 5) Compared with the screening period, the ulcer area was reduced = 20% at randomization, or the ulcer had a significant improvement trend based on the judgement of investigator. 6) The ischemic limb was not suitable for multi-sites intramuscular injection based on judgement of investigator. 7) Patients with a revascularization procedure or sympathectomy or amputation within 4 weeks prior to sign informed consent. 2. Existing the following diseases or treatment history: 1) Previously been diagnosed with diabetic retinopathy or other proliferative retinopathy or cannot undergo retinopathy testing. 2) Have a previous history of malignant tumors, or suspected tumor risk judged by investigators during screening. 3) Have used gene and cell therapy or participated in clinical trials related to gene and cell therapy. 4) Heart Failure with a NYHA classification of III or IV. 5) Previous diagnosis of severe arrhythmias, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate. 6) Severe liver disease, such as cirrhosis with jaundice and ascites, at the time of screening or randomization. 7) Have a history of major surgery within 3 months prior to screening or plan to have major surgery during the study period. 8) Participated in clinical trials of other drug interventions within 3 months prior to screening (except for unsuccessful screening). 9) Patients with cerebral infarction, cerebral hemorrhage, myocardial infarction, and 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) A history of drug abuse or alcohol abuse. 12) Suspected allergic history to the experimental drug or any component of the experimental 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 determined by the investigator to be unsuitable for clinical trials. 14) Pregnancy test positive. 3. General condition: 1) Can not correctly describe symptoms and emotions. 2) Life expectancy assessed by the investigator to be less than 2 years or possible amputation during the study period. 3) Male or female who do not agree to use highly effective contraception during the study period and for 6 months after the last dose. 4) Pregnant or lactating women. 5) The investigator determines that the patient has poor compliance or has any factors that would preclude participation in the study, including, but not limited to, that the study places the patient at unacceptable risk or may interfere with the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability;Long-term safety of multiple dose;Long-term efficacy of multiple dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in pharmacokinetics and immunogenicity;Initial effectiveness after multiple dosing; | — |
Countries
China
Contacts
Public ContactWeiguo Fu
Zhongshan Hospital Affiliated to Fudan University
Outcome results
None listed