Status:

COMPLETED

Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia (NL003-CLI-III-1)

Lead Sponsor:

Beijing Northland Biotech. Co., Ltd.

Conditions:

Arterial Occlusive Disease

Ischemia

Eligibility:

All Genders

20-80 years

Phase:

PHASE3

Brief Summary

To evaluate the safety and efficacy of recombinant human hepatocyte growth factor (HGF) bare plasmid injection for local intramuscular injection in the treatment of patients with severe lower limb hem...

Detailed Description

Management of CLI process consumes a significant amount of healthcare resources,and the new therapeutic approaches are required. Hepatocyte growth factor (HGF) has been shown to be a potent angiogeni...

Eligibility Criteria

Inclusion

  • 1\. Age 20 and 80 (when signing informed consent), both male and female;
  • 2\. Patients diagnosed with lower limb arterial ischemic disease based on DSA or CTA and combined with their medical history and clinical manifestations and Rutherford grade 4 (resting pain) must meet the following criteria simultaneously (if both limbs of the subject have lower limb arterial ischemic disease, the researcher shall choose one limb for the study).Resting ankle systolic pressure (dorsal foot artery or posterior tibial artery) ≤70mmHg or ABI≤0.5 or TcPO2 \< 30mmHg;In the first 3 months after randomized inclusion, DSA or CTA confirmed severe stenosis (≥70%) or occlusion of superficial femoral artery or popliteal artery or inferior knee artery.
  • 3\. Chronic lower limb arterial ischemia combined with resting pain met the following requirements: resting pain lasted for more than 2 weeks when the informed consent was signed;
  • 4\. Agreed to use the basic treatment drugs as required during the trial, and recorded the daily record of the subjects in a timely and complete manner. The compliance of the basic treatment drugs and the subjects' diary filling during the screening period was 70%.
  • 5\. Agree to use appropriate contraceptive measures during the experiment;Female subjects of reproductive age, blood pregnancy test negative;
  • 6\. Signed informed consent

Exclusion

  • 1\. Patients with acute lower limb ischemia or acute exacerbation of chronic lower limb ischemia.
  • 2\. Vascular reconstruction (bypass or intravascular therapy) or sympathetic resection or amputation was performed within 4 weeks prior to the signing of the informed consent.
  • 3\. Due to surgical operation, the patient is still in the postoperative risk period, and the researcher judges that the patient is not suitable for the test.
  • 4\. Main-iliac artery stenosis 70%.
  • 5\. Patients with ischemic ulcer of lower extremity.
  • 6\. NYHA classification of cardiac function is classified as grade (see annex 1 for specific classification criteria).
  • 7\. Patients with unstable angina pectoris due to cerebral infarction, cerebral hemorrhage and myocardial infarction within 3 months before signing the informed consent.
  • 8\. Refractory hypertension (taking three or more antihypertensive drugs, systolic blood pressure 180mmHg or diastolic blood pressure 110mmHg).
  • 9\. Proliferative retinopathy and retinopathy examination is not available.
  • 10\. Inability to accurately describe symptoms and emotions.
  • 11\. Severe liver disease with uncompensated cirrhosis, jaundice, ascites or hemorrhagic varices.
  • 12\. Current recipients of immunosuppressants or chemoradiotherapy.
  • 13\. Anti-hiv antibody positive, anti-hepatitis c antibody positive and hepatitis b surface antigen positive (if the subject is HBsAg positive and HBV DNA in peripheral blood is combined, the researcher believes that the subject's chronic hepatitis b is stable and will not increase the risk of the subject, the subject can be selected).
  • 14\. Results of laboratory examination during screening period: hemoglobin \<80g/L, white blood cell count \< 3.0109 /L, platelet \<75 109/L, upper limit of normal AST or ALT\> 3 times, upper limit of normal serum creatinine \> 2.5 times, or other laboratory examination indicators appear abnormal that researchers think may affect the evaluation of test results.
  • 15\. Patients with poor blood glucose control after treatment (hemoglobin a1c \>10%).
  • 16\. Previously diagnosed with malignant tumor, or any of the following test results determined by the investigator to be at risk of tumor: fecal occult blood test;Chest X-ray examination or chest CT examination;Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and ca19-9;Male subjects, prostate specific antigen test (PSA, free PSA);Female subjects, cervical smear (Pap), mammography/b-ultrasound and ca-125 examination;The investigators determined that additional tests were necessary to eliminate the tumor risk.
  • 17\. In the opinion of the investigators, patients with comorbidities that affect safety and efficacy evaluation, or with a predicted survival of less than 12 months.
  • 18\. Frequent drinkers within the 12 months prior to the signing of the informed consent, i.e., those who drank more than 14 units of alcohol per week (1 unit =360 mL beer or 45 mL alcohol of 40% spirits or 150 mL wine) or substance abusers.
  • 19\. Participate in other clinical trials within 3 months before signing the informed consent.

Key Trial Info

Start Date :

August 2 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

June 3 2024

Estimated Enrollment :

302 Patients enrolled

Trial Details

Trial ID

NCT04275323

Start Date

August 2 2019

End Date

June 3 2024

Last Update

September 19 2024

Active Locations (13)

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Page 1 of 4 (13 locations)

1

Beijing Hospitai

Beijing, Beijing Municipality, China, 100005

2

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China, 100032

3

The Ninth People's Hospital of Chongqing

Chongqing, Chongqing Municipality, China, 400700

4

Zhangzhou Municipal Hospital of Fujian Province

Zhangzhou, Fujian, China, 363000