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

B

Beijing Northland Biotech

Status and phase

Completed
Phase 2

Conditions

Peripheral Vascular Disease
Ischemia
Arterial Occlusive Disease
Ulcers

Treatments

Genetic: NL003
Other: Normal Saline

Study type

Interventional

Funder types

Industry

Identifiers

NCT01548378
NL003CLI-II

Details and patient eligibility

About

The purpose of this study is to evaluate whether intramuscular injections of NL003 into the calf is safe and effective in the treatment of critical limb ischemia

Full 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 angiogenic growth factor stimulating the growth of endothelial cells and migration of vascular smooth muscle cells. Because of its pluripotent capabilities, increasing the availability of HGF in ischemic tissues to achieve therapeutic angiogenesis has been a growing area of research. This study will use 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. As there are currently no approved drugs that can reverse CLI and as most patients have exhausted surgical and endovascular intervention options, inducing angiogenesis in the affected limb with NL003 may result in an increase in tissue perfusion, which, in turn improve wound healing, reduce pain and improve limb salvage rates.

Enrollment

200 patients

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

200 participants in 4 patient groups, including a placebo group

High Dose
Experimental group
Description:
Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
Treatment:
Genetic: NL003
Middle Dose
Experimental group
Description:
Patients in this treatment group will receive 6mg NL003 respective in D0、14、28
Treatment:
Genetic: NL003
Low Dose
Experimental group
Description:
Patients in this treatment group will receive 4mg NL003 in D0、14、28
Treatment:
Genetic: NL003
Placebo
Placebo Comparator group
Description:
Patients in this group will receive normal saline respective in D0、14、18
Treatment:
Other: Normal Saline

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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