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Trial record 1 of 6 for:    NL003
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Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia (NL003CLI-II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01548378
Recruitment Status : Completed
First Posted : March 8, 2012
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Beijing Northland Biotech. Co., Ltd.

Tracking Information
First Submitted Date  ICMJE March 5, 2012
First Posted Date  ICMJE March 8, 2012
Last Update Posted Date January 22, 2020
Study Start Date  ICMJE March 2012
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2015)
  • The difference in ulcer area between baseline and the D180. [ Time Frame: Day180 ]
    Rutherford 5 only
  • The difference in pain level between baseline and the D180 as determined by VAS [ Time Frame: Day 180 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 5, 2012)
  • To assess the difference in ulcer area between baseline and the D180. [ Time Frame: Day180 ]
  • To assess the difference in pain level between baseline and the D180 as determined by VAS [ Time Frame: Day 180 ]
Change History Complete list of historical versions of study NCT01548378 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2012)
  • Change in tissue oxygenation (TcPO2) from baseline to D180 [ Time Frame: Day0、14、28、60、90、180 ]
  • Difference in percentage of pain level decreased by 50% determined by VAS from baseline to D180 [ Time Frame: Day0、14、28、60、90、180 ]
  • Difference in percentage of ulcer area decreased by 50% from baseline to D180 [ Time Frame: Day0、14、28、60、90、180 ]
  • Difference in ABI and TBI from baseline to D180 [ Time Frame: Day0、14、28、60、90、180 ]
  • Difference in QOL score (VascuQol) from baseline to D180 [ Time Frame: Day0、14、28、60、90、180 ]
  • Percentage of ulcer complete healing [ Time Frame: Day180 ]
  • Situation of ulcer healing [ Time Frame: Day180 ]
  • Ulcer healing after gangrene treatment [ Time Frame: Day180 ]
  • Major amputation rate [ Time Frame: Day180 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia
Official Title  ICMJE A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of NL003 in Subject With Critical Limb Ischemia
Brief Summary 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
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Arterial Occlusive Disease
  • Ulcers
  • Ischemia
  • Peripheral Vascular Disease
Intervention  ICMJE
  • Genetic: NL003
    Day 0: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 14: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 28: 8mg of NL003 (32 injections of 0.5ml of NL003)
    Other Names:
    • HGF plasmid
    • pCK-HGF-X7
  • Genetic: NL003
    Day 0: 6mg of NL003 (24 injections of 0.5ml of NL003) and 4ml normal saline(8 injections) Day 14: 6mg of NL003 (24 injections of 0.5ml of NL003) and 4ml normal saline(8 injections) Day 28: 6mg of NL003 (24 injections of 0.5ml of NL003) and 4ml normal saline(8 injections)
    Other Names:
    • HGF plasmid
    • pCK-HGF-X7
  • Genetic: NL003
    Day 0: 4mg of NL003 (16 injections of 0.5ml of NL003) and 8ml normal saline(16 injections) Day 14: 4mg of NL003 (16 injections of 0.5ml of NL003) and 8ml normal saline(16 injections) Day 28: 4mg of NL003 (16 injections of 0.5ml of NL003) and 8ml normal saline(16 injections)
    Other Names:
    • HGF plasmid
    • pCK-HGF-X7
  • Other: Normal Saline
    Day 0: 16ml of Normal Saline (32 injections ) Day 14: 16ml of Normal Saline (32 injections ) Day 28: 16ml of Normal Saline (32 injections )
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: High Dose
    Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
    Intervention: Genetic: NL003
  • Experimental: Middle Dose
    Patients in this treatment group will receive 6mg NL003 respective in D0、14、28
    Intervention: Genetic: NL003
  • Experimental: Low Dose
    Patients in this treatment group will receive 4mg NL003 in D0、14、28
    Intervention: Genetic: NL003
  • Placebo Comparator: Placebo
    Patients in this group will receive normal saline respective in D0、14、18
    Intervention: Other: Normal Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2012)
200
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01548378
Other Study ID Numbers  ICMJE NL003CLI-II
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Beijing Northland Biotech. Co., Ltd.
Study Sponsor  ICMJE Beijing Northland Biotech. Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Beijing Northland Biotech. Co., Ltd.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP