A Double-Blind, Randomized, Placebo-Controlled, Single Center Study to Assess the Angiogenesis and Blood Perfusion Effect of NL003 in Patients With Critical Limb Ischemia by PETCT-RGD and MIBI
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Changes of the new blood vessels number
研究概览
简要总结
The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the angiogenesis assessment of NL003 in PAD patients.
详细描述
Hepatocyte growth factor (HGF) gene therapy has been shown to be a potential choice for CLI patients without surgical option. NL003, which is a DNA plasmid that contains novel genomic cDNA hybrid human HGF coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and HGF 723. Animal studies showed that NL003 inducing angiogenesis in the affected limb and result in an increase in tissue perfusion. Our previous phase II clinical trial has suggested the successful limb-salvaging capacity of NL003 in treatment of patients with CLTI.
In this study we will use 68Ga RGD PET/CT and 99mTc MIBI SPECT imaging methods to evaluate the effect of NL003 on angiogenesis and lower limb blood flow perfusion during the treatment of chronic lower limb ischemia, and evaluated the effectiveness and safety of the drug. The subjects will be randomly divided into the investigational drug group and the placebo group in a 1:1 ratio. NL003 or placebo will be injected into the muscle of the affected limb on D0, D14 and D28, 0.5mg/0.5mL/site, total 8mg, 32 sites. PET/CT will be measured on D14, D42 before drug administration, MIBI SPECT imaging will be collected on D60.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-80 years, diagnosed with chronic lower limb ischemia;
- •According to DSA or CTA，severe stenosis (≥70%) or occlusion of one or more branches of superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery, and peroneal artery.
- •Patients with obvious symptoms of lower limb ischemia, including severe claudication, resting pain, ulcers, or gangrene.
- •Agree to use appropriate contraceptive methods during the trial; Female subjects of reproductive age, blood pregnancy test negative.
- •Signing the informed consent.
- •Can complete PETCT-RGD check and MIBI check;
排除标准
- •The foot or lower limb infection cannot be controlled, and amputation may be accepted within 3 months.
- •Those with cerebral infarction, cerebral hemorrhage, heart failure, unstable angina, acute myocardial infarction, and serious arrhythmia within 3 months;
- •Tumor patients diagnosed with malignant tumor or suspected of having malignant tumor after tumor screening;
- •Main iliac artery stenosis ≥ 70%;
- •Refractory hypertension (taking three or more antihypertensive drugs, systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 110mmHg);
- •Anti HIV antibody positive person, anti hepatitis C antibody positive person and RNA positive person, hepatitis B surface antigen positive person (if the subject is HBsAg positive, and judging by peripheral blood HBV DNA, the researcher believes that the subject is in a stable period of chronic hepatitis B, which will not increase the risk of the subject, the subject can be selected)
- •Patients with poor blood glucose control after treatment (HbA1c>10%);
- •Persons allergic to contrast medium
- •The investigator believes that the patient's complications affect the evaluation of safety and effectiveness, or the expected survival period is less than 12 months;
- •Those who regularly drink more than 14 units of alcohol (1 unit=360 mL beer or 45 mL liquor or 150 mL wine with 40% alcohol) or drug abusers within 12 months before signing the informed consent form;
- •Acute lower limb ischemia or acute aggravation of chronic lower limb ischemia;
- •Those who received vascular reconstruction of the affected limb within 4 weeks before the informed consent form and whose blood supply improved after the operation
- •Serious liver or kidney disease or severe anemia judged by the investigator;
- •Those who cannot correctly describe symptoms and emotions;
- •Those who participated in other clinical trials within 3 months before signing the informed consent form.
研究组 & 干预措施
investigational product
Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
干预措施: NL003 (Drug)
Placebo
Patients in this group will receive normal saline respective in D0、14、28
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of the new blood vessels number
时间窗: Day 14、Day 42
changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
Changes of local blood perfusion
时间窗: Day 60
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
次要结局
- Changes to the ABI from the baseline(Day 60)
- Laser Speckle Imaging changes in blood flow from the baseline(Day 60)
- Changes of pain score from the baseline(Day 14、Day 28、Day 42、Day 60、Day 90)
- Gangrene /Ulcer changes from the baseline(Day 14、Day 28、Day 42、Day 60、Day 90)
- Changes in quality of life scores from baseline(Day 60)