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Arterial Occlusive DiseasePhase 3NCT04275323

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

A Phase 3 study testing NL003 and Normal Saline in people with Arterial Occlusive Disease and Ischemia, run by Beijing Northland Biotech. Co., Ltd. at 13 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

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 hemorrhagic disease (Rutherford grade 4) Read more about this study

Who is it for?
Ages 20 to 80 years
Conditions the study is for
Arterial Occlusive Disease, Ischemia, Ulcers
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
302 participants
Where
13 sitesChina
Study dates
2 Aug 2019to 3 Jun 2024
Phase
Phase 3
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 20 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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).
Show all 19Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

China13 sites

  • Beijing Hospitai

    Beijing, Beijing Municipality, 100005

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100032

  • The Second Xiangya Hospital of Central South University

    Changsha, Hunan, 410000

  • The Third Xiangya Hospital of Central South University

    Changsha, Hunan, 410000

  • Chifeng Municipal Hospital

    Chifeng, Neimenggu, 024000

  • The Ninth People's Hospital of Chongqing

    Chongqing, Chongqing Municipality, 400700

  • The Affiliated Hospital of Qingdao University

    Qingdao, Shandong, 266003

  • Shanghai seventh people's hospital

    Shanghai, Shanghai Municipality, 200120

  • Shanxi Provincial People's Hospital

    Taiyuan, Shanxi, 030012

  • First Affiliated Hospital of Xi 'an Jiaotong University

    XiAn, Shanxi, 710061

  • Second Affiliated Hospital of Xi 'an Jiaotong University

    XiAn, Shanxi, 710061

  • Xuzhou Mining Group General Hospital

    Xuzhou, Jiangsu, 221006

  • Zhangzhou Municipal Hospital of Fujian Province

    Zhangzhou, Fujian, 363000

Other trials in China

About this study

Official title: A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of NL003 in Subject With Critical Limb Ischemia(Rutherford 4)

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 hemorrhagic disease (Rutherford grade 4)

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, Ischemia, Ulcer, 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)

  • 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 NCT04275323
Study groupRoleWhat they receive
investigational producExperimentalPatients in this treatment group will receive 8mg NL003 respective 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. Complete pain relief rate

    1.Day180 visit (5-7 days prior to visit, including the visit day), mean daily pain score was 0；2.A pain score of 0 must be measured without the use of analgesics.

    Measured: Day180

Secondary outcomes (9)

  1. The time when the pain completely goes away

    The time when the pain completely goes away.

    Measured: Day180

  2. Complete pain relief rate

    Day90 visit (5-7 days prior to visit, including the visit day), mean daily pain score was 0.

    Measured: Day90

  3. Changes in site visits, pain scores after use of the study drug

    The Numerical Rating Scale（NRS） was used to record changes in pain in subjects, who chose a number that best represented their pain in the past 24 hours, ranging from 0 (painless) to 10 (the most intense pain imaginable).The NRS scale is pain free (0), mild pain (1-3), moderate pain (4-6), and severe pain (7-10).

    Measured: Day14,Day28,Day60,Day90,Day120,Day180

  4. Percent of Participants with a 50% reduction in pain score from baseline

    Percent of Participants with a 50% reduction in pain score from baseline.

    Measured: Day180

  5. The type and dose of analgesics varied from baseline

    The types and dosages of analgesics varied from baseline at each site after the use of the study drug.

    Measured: Day14,Day28,Day60,Day90,Day120,Day180

  6. Changes in Rutherford grading from baseline to Day180

    The severity of critical Limb ischemia was assessed by Rutherford grading at screening, D14, D28, D60, D90, and D180, respectively.Rutherford grades chronic limb ischemic disease into grades 0 to 6, of which 4, 5 and 6 are chronic severe ischemia.

    Measured: Day14,Day28,Day60,Day90,Day120,Day180

  7. Changes in quality of life scores from baseline to Day180

    The WHOQOL-BREF was conducted to evaluate the subjective perception of Critical Limb Ischemia, including the subjects' perception of quality of life, health, or other aspects of life.The whoqol-bref has 26 questions. Each question is rated on a scale of 1 to 5, with 1 for poor quality of life and 5 for good quality of life.

    Measured: Day14,Day28,Day60,Day90,Day120,Day180

  8. Changes in the ABI from the baseline to Day180

    Ankle-brachial index (ABI) refers to the ratio of systolic blood pressure of the anterior tibial artery (dorsal foot artery) or posterior tibial artery to the systolic blood pressure of the brachial artery.Participants were tested for ankle-brachial index (ABI).The normal value of ABI is 0.9-1.4, where <0.4 is severe ischemia,0.41-0.9 is mild to moderate ischemia, and ABI>1.4 indicates vascular wall calcification.

    Measured: Day60,Day90,Day120,Day180

  9. Percentage of patients who underwent revascularization (open surgery or interventional therapy) had a large amputation rate and mortality

    Day180, percentage of patients undergoing revascularization (open surgery or interventional therapy) major amputation rate mortality.

    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 posted19 Feb 2020
  2. Study start2 Aug 2019
  3. Primary completion3 Jun 2024
  4. Study completion3 Jun 2024

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
302 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04275323
Sponsor's protocol ID
NL003-CLI-III-1
Status last verified
Mar 2022
First submitted
18 Jan 2020
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NL003 and Normal Saline in people with Arterial Occlusive Disease and Ischemia, run by Beijing Northland Biotech. Co., Ltd. at 13 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 6 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Complete pain relief rate (time frame: Day180). 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 NCT04275323.

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 19 Sep 2024.

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