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Arterial Occlusive DiseasePhase 2NL003CLI-IINCT01548378

Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia

A Phase 2 study testing NL003 and Normal Saline in people with Arterial Occlusive Disease and Ulcers, run by Beijing Northland Biotech. Co., Ltd. at 9 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 30 to 80 years
Conditions the study is for
Arterial Occlusive Disease, Ulcers, Ischemia
What is being tested?
NL003 and Normal Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
9 sitesChina
Study dates
Mar 2012to Jun 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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 locations and contacts

9 sites in 1 country.

9 sites in 1 country

China9 sites

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100032

  • Beijing Shijitan Hospital

    Beijing, Beijing Municipality, 100038

  • Xuanwu Hospital Capital Medical University

    Beijing, Beijing Municipality, 100053

  • The General Hospital of the People's Liberation Army

    Beijing, Beijing Municipality, 100853

  • First Hospital of Jilin University

    Changchun, Jilin, 130021

  • The Second Xiangya Hospital of Central South University

    Changsha, Hunan

  • The Second Hospital of Dalian Medical University

    Dalian, Liaoning

  • Nanjing Drum Tower Hospital

    Nanjing, Jiangsu, 210008

  • Wuhan Union Hospital

    Wuhan, Hubei, 430022

Other trials in China

About this study

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

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

Read the 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.

Being tested
NL003, Normal Saline
Keywords
HGF, Gene, Critical Limb Ischemia
Medical subject headings
Arterial Occlusive Diseases, Ulcer, Ischemia, Peripheral Vascular Diseases, Chronic Limb-Threatening Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NL003Genetic

    Also called HGF plasmid, pCK-HGF-X7

    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)

  • NL003Genetic

    Also called HGF plasmid, pCK-HGF-X7

    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)

  • NL003Genetic

    Also called HGF plasmid, pCK-HGF-X7

    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)

  • Normal SalineOther

    Also called Placebo

    Day 0: 16ml of Normal Saline (32 injections ) Day 14: 16ml of Normal Saline (32 injections ) Day 28: 16ml of Normal Saline (32 injections )

Study groups in NCT01548378
Study groupRoleWhat they receive
High DoseExperimentalPatients in this treatment group will receive 8mg NL003 respective in D0、14、28
Receives: Genetic: NL003
Middle DoseExperimentalPatients in this treatment group will receive 6mg NL003 respective in D0、14、28
Receives: Genetic: NL003
Low DoseExperimentalPatients in this treatment group will receive 4mg NL003 in D0、14、28
Receives: Genetic: NL003
PlaceboPlacebo comparatorPatients in this group will receive normal saline respective in D0、14、18
Receives: Other: Normal Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The difference in ulcer area between baseline and the D180.

    Rutherford 5 only

    Measured: Day180

  2. The difference in pain level between baseline and the D180 as determined by VAS

    Measured: Day 180

Secondary outcomes (9)

  1. Change in tissue oxygenation (TcPO2) from baseline to D180

    Measured: Day0、14、28、60、90、180

  2. Difference in percentage of pain level decreased by 50% determined by VAS from baseline to D180

    Measured: Day0、14、28、60、90、180

  3. Difference in percentage of ulcer area decreased by 50% from baseline to D180

    Measured: Day0、14、28、60、90、180

  4. Difference in ABI and TBI from baseline to D180

    Measured: Day0、14、28、60、90、180

  5. Difference in QOL score (VascuQol) from baseline to D180

    Measured: Day0、14、28、60、90、180

  6. Percentage of ulcer complete healing

    Measured: Day180

  7. Situation of ulcer healing

    Measured: Day180

  8. Ulcer healing after gangrene treatment

    Measured: Day180

  9. Major amputation rate

    Measured: Day180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionJun 2014
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01548378
Sponsor's protocol ID
NL003CLI-II
Acronym
NL003CLI-II
Status last verified
Jan 2020
First submitted
5 Mar 2012
Last updated
22 Jan 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NL003 and Normal Saline in people with Arterial Occlusive Disease and Ulcers, run by Beijing Northland Biotech. Co., Ltd. at 9 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The difference in ulcer area between baseline and the D180. (time frame: Day180). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01548378.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020; AzTrials last refreshed its copy on 30 Oct 2026.

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