Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia (NL003CLI-II)

This is an interventional treatment trial for Arterial Occlusive Disease focused on measuring HGF, Gene, Critical Limb Ischemia Read More

Inclusion Criteria:

• Male or female, between 30 and 80years of age

• Diagnosis of critical limb ischemia(ASO、TAO、DAO)，Rutherford Class 4 or 5, including:

  • A resting ankle systolic pressure of ≤ 70 mmHg in the affected limb; or
  • A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or
  • For patients in which measurement of ankle systolic pressure is not feasible , TcPO2 ≤ 30mmHg; Only unilateral affected limb receive treatment。
• Significant stenosis (≥ 75%) of one or more of the following arteries:

superficial femoral, popliteal as verified by angiography（DSA、CTA、MRA） within 12 months prior to enrollment

• Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study
• Be willing to maintain ulcer treatment
• Be willing to infertility throughout the course of the study
• If the subject is of child-bearing potential, she must have a negative urine pregnancy test result prior to study enrollment
• Tumor screening result is no clinic meaning，including:
• Signing the informed consent document prior to being subjected to any study related procedures

Exclusion Criteria:

• Subjects who have undergone a successful revascularization procedure or sympathectomy within 12 weeks prior to study entry.
• Acute advanced CLI
• Subjects that will require an amputation in the target leg within 4 weeks, or significant stenosis (≥ 75%) of Aortoiliac
• Subjects with evidence of active infection or deep ulceration exposing bone or tendon in the extremity planned for treatment
• Heart Failure with a NYHA classification of III or IV
• Stroke、myocardial infarction or unstable angina within last 3 months
• Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination
• Can not correctly describe the symptoms and feeling
• Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites or bleeding varices
• Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy
• Positive HIV,active Hepatitis B(determined by HBsAb\ HBcAb\HBsAg) or C infection
• Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary
• Elevated PSA unless prostate cancer has been excluded
• Patients with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings
• Subjects requiring > 100 mg daily of acetylsalicylic acid,COX-2 inhibitor drug(s) or high dose steroids (excepting inhaled steroids)
• Subjects with any co- morbid conditions likely to interfere with assessment of safety or efficacy or with an estimated life expectancy of less than 12 months
• History of drug or alcohol abuse / dependence in the past 12 months
• Use of an investigational drug or treatment in past 3 months