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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01548378
First Posted: March 8, 2012
Last Update Posted: March 25, 2015
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.
Collaborator:
ViroMed Co., Ltd. dba VM BioPharma
Information provided by (Responsible Party):
Beijing Northland Biotech. Co., Ltd.
  Purpose
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

Condition Intervention Phase
Arterial Occlusive Disease Ulcers Ischemia Peripheral Vascular Disease Genetic: NL003 Other: Normal Saline Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of NL003 in Subject With Critical Limb Ischemia

Further study details as provided by Beijing Northland Biotech. Co., Ltd.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 200
Study Start Date: March 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose
Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
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
Experimental: Middle Dose
Patients in this treatment group will receive 6mg NL003 respective in D0、14、28
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
Experimental: Low Dose
Patients in this treatment group will receive 4mg NL003 in D0、14、28
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
Placebo Comparator: Placebo
Patients in this group will receive normal saline respective in D0、14、18
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

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   30 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01548378


Locations
China, Beijing
Peking Union Medical College Hospital
Beijing, Beijing, China, 100032
Beijing Shijitan Hospital
Beijing, Beijing, China, 100038
Xuanwu Hospital Capital Medical University
Beijing, Beijing, China, 100053
The General Hospital of the People's Liberation Army
Beijing, Beijing, China, 100853
China, Hubei
Wuhan Union Hospital
Wuhan, Hubei, China, 430022
China, Hunan
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
China, Jiangsu
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China, 210008
China, Jilin
First Hospital of Jilin University
Changchun, Jilin, China, 130021
China, Liaoning
The Second Hospital of Dalian Medical University
Dalian, Liaoning, China
Sponsors and Collaborators
Beijing Northland Biotech. Co., Ltd.
ViroMed Co., Ltd. dba VM BioPharma
  More Information

Additional Information:
Responsible Party: Beijing Northland Biotech. Co., Ltd.
ClinicalTrials.gov Identifier: NCT01548378     History of Changes
Other Study ID Numbers: NL003CLI-II
First Submitted: March 5, 2012
First Posted: March 8, 2012
Last Update Posted: March 25, 2015
Last Verified: March 2015

Keywords provided by Beijing Northland Biotech. Co., Ltd.:
HGF
Gene
Critical Limb Ischemia

Additional relevant MeSH terms:
Ischemia
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Arterial Occlusive Diseases
Pathologic Processes
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis