Peripheral Artery DiseasePhase 3NCT05968118
Angiogenesis and Blood Perfusion Effect of HGF Gene Therapy in PAD Patients
A Phase 3 study testing NL003 in people with Peripheral Artery Disease, run by Beijing Northland Biotech. Co., Ltd. at 1 site in China.
Trial summary
The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the angiogenesis assessment of NL003 in PAD patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Peripheral Artery Disease
- What is being tested?
- NL003
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 29 Jul 2022to 31 Oct 2023
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-80 years, diagnosed with chronic lower limb ischemia;
- According to DSA or CTA，severe stenosis (≥70%) or occlusion of one or more branches of superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery, and peroneal artery.
- Patients with obvious symptoms of lower limb ischemia, including severe claudication, resting pain, ulcers, or gangrene.
- Agree to use appropriate contraceptive methods during the trial; Female subjects of reproductive age, blood pregnancy test negative.
- Signing the informed consent.
- Can complete PETCT-RGD check and MIBI check;
Who cannot join
- The foot or lower limb infection cannot be controlled, and amputation may be accepted within 3 months.
- Those with cerebral infarction, cerebral hemorrhage, heart failure, unstable angina, acute myocardial infarction, and serious arrhythmia within 3 months;
- Tumor patients diagnosed with malignant tumor or suspected of having malignant tumor after tumor screening;
- Main iliac artery stenosis ≥ 70%;
- Refractory hypertension (taking three or more antihypertensive drugs, systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 110mmHg);
- Anti HIV antibody positive person, anti hepatitis C antibody positive person and RNA positive person, hepatitis B surface antigen positive person (if the subject is HBsAg positive, and judging by peripheral blood HBV DNA, the researcher believes that the subject is in a stable period of chronic hepatitis B, which will not increase the risk of the subject, the subject can be selected)
Show all 15Show fewer
- Patients with poor blood glucose control after treatment (HbA1c>10%);
- Persons allergic to contrast medium
- The investigator believes that the patient's complications affect the evaluation of safety and effectiveness, or the expected survival period is less than 12 months;
- Those who regularly drink more than 14 units of alcohol (1 unit=360 mL beer or 45 mL liquor or 150 mL wine with 40% alcohol) or drug abusers within 12 months before signing the informed consent form;
- Acute lower limb ischemia or acute aggravation of chronic lower limb ischemia;
- Those who received vascular reconstruction of the affected limb within 4 weeks before the informed consent form and whose blood supply improved after the operation
- Serious liver or kidney disease or severe anemia judged by the investigator;
- Those who cannot correctly describe symptoms and emotions;
- Those who participated in other clinical trials within 3 months before signing the informed consent form.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100032
Changwei Liu
Xiao Di
About this study
Official title: A Double-Blind, Randomized, Placebo-Controlled, Single Center Study to Assess the Angiogenesis and Blood Perfusion Effect of NL003 in Patients With Critical Limb Ischemia by PETCT-RGD and MIBI
The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the angiogenesis assessment of NL003 in PAD patients.
Read the detailed description
Hepatocyte growth factor (HGF) gene therapy has been shown to be a potential choice for CLI patients without surgical option. 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. Animal studies showed that NL003 inducing angiogenesis in the affected limb and result in an increase in tissue perfusion. Our previous phase II clinical trial has suggested the successful limb-salvaging capacity of NL003 in treatment of patients with CLTI.
In this study we will use 68Ga RGD PET/CT and 99mTc MIBI SPECT imaging methods to evaluate the effect of NL003 on angiogenesis and lower limb blood flow perfusion during the treatment of chronic lower limb ischemia, and evaluated the effectiveness and safety of the drug. The subjects will be randomly divided into the investigational drug group and the placebo group in a 1:1 ratio. NL003 or placebo will be injected into the muscle of the affected limb on D0, D14 and D28, 0.5mg/0.5mL/site, total 8mg, 32 sites. PET/CT will be measured on D14, D42 before drug administration, MIBI SPECT imaging will be collected on D60.
- Conditions
- Peripheral Artery Disease
- Being tested
- NL003, Placebo
- Keywords
- Peripheral Artery Disease, Hepatocyte Growth Factor, NL003, Gene therapy, PET/CT-RGD, MIBI
- Medical subject headings
- Peripheral Arterial Disease, Deafness, Autosomal Recessive 39
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NL003Drug
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)
PlaceboDrug
Also called 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 group | Role | What they receive |
|---|---|---|
| investigational product | Experimental | Patients in this treatment group will receive 8mg NL003 respective in D0、14、28 Receives: Drug: NL003 |
| Placebo | Placebo comparator | Patients in this group will receive normal saline respective in D0、14、28 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of the new blood vessels number
changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
Measured: Day 14、Day 42
Changes of local blood perfusion
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
Measured: Day 60
Secondary outcomes (5)
Changes to the ABI from the baseline
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).
Measured: Day 60
Laser Speckle Imaging changes in blood flow from the baseline
Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.
Measured: Day 60
Changes of pain score from the baseline
The severity of critical Limb ischemia was assessed by Rutherford grading at screening、D14、D28、D42、D60、D90
Measured: Day 14、Day 28、Day 42、Day 60、Day 90
Gangrene /Ulcer changes from the baseline
Changes in the area of ulcer or gangrene from baseline after use of the study drug
Measured: Day 14、Day 28、Day 42、Day 60、Day 90
Changes in quality of life scores from baseline
The quality of life score questionnaire 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.
Measured: Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start29 Jul 2022
- Primary completion31 Jul 2023 (estimated)
- Study completion31 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Northland Biotech. Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05968118
- Sponsor's protocol ID
- NL003-PAD-III-3
- Status last verified
- Jul 2023
- First submitted
- 4 Jan 2023
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-Controlled, Single Center Study to Assess the Angiogenesis and Blood Perfusion Effect of NL003 in Patients With Critical Limb Ischemia by PETCT-RGD and MIBI
- ClinicalTrials.gov ID
- NCT05968118
- Acronym / sponsor ID
- NL003-PAD-III-3
- Conditions
- Peripheral Artery Disease
- Keywords
- Peripheral Artery Disease, Hepatocyte Growth Factor, NL003, Gene therapy, PET/CT-RGD, MIBI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Beijing Northland Biotech. Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 29 Jul 2022 (actual)
- Primary completion
- 31 Jul 2023 (estimated)
- Study completion
- 31 Oct 2023 (estimated)
- First posted
- 1 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the angiogenesis assessment of NL003 in PAD patients.
Detailed description
Hepatocyte growth factor (HGF) gene therapy has been shown to be a potential choice for CLI patients without surgical option. 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. Animal studies showed that NL003 inducing angiogenesis in the affected limb and result in an increase in tissue perfusion. Our previous phase II clinical trial has suggested the successful limb-salvaging capacity of NL003 in treatment of patients with CLTI.
In this study we will use 68Ga RGD PET/CT and 99mTc MIBI SPECT imaging methods to evaluate the effect of NL003 on angiogenesis and lower limb blood flow perfusion during the treatment of chronic lower limb ischemia, and evaluated the effectiveness and safety of the drug. The subjects will be randomly divided into the investigational drug group and the placebo group in a 1:1 ratio. NL003 or placebo will be injected into the muscle of the affected limb on D0, D14 and D28, 0.5mg/0.5mL/site, total 8mg, 32 sites. PET/CT will be measured on D14, D42 before drug administration, MIBI SPECT imaging will be collected on D60.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| investigational product | Experimental | Drug: NL003Patients in this treatment group will receive 8mg NL003 respective in D0、14、28 |
| Placebo | Placebo comparator | Drug: PlaceboPatients in this group will receive normal saline respective in D0、14、28 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18-80 years, diagnosed with chronic lower limb ischemia;
- According to DSA or CTA，severe stenosis (≥70%) or occlusion of one or more branches of superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery, and peroneal artery.
- Patients with obvious symptoms of lower limb ischemia, including severe claudication, resting pain, ulcers, or gangrene.
- Agree to use appropriate contraceptive methods during the trial; Female subjects of reproductive age, blood pregnancy test negative.
- Signing the informed consent.
Key exclusion criteria (15 listed)
- The foot or lower limb infection cannot be controlled, and amputation may be accepted within 3 months.
- Those with cerebral infarction, cerebral hemorrhage, heart failure, unstable angina, acute myocardial infarction, and serious arrhythmia within 3 months;
- Tumor patients diagnosed with malignant tumor or suspected of having malignant tumor after tumor screening;
- Main iliac artery stenosis ≥ 70%;
- Refractory hypertension (taking three or more antihypertensive drugs, systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 110mmHg);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NL003Also: HGF plasmid, pCK-HGF-X7Day 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) | Drug | investigational product |
| PlaceboAlso: Normal SalineDay 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 | Drug | Placebo |
Primary outcome
Changes of the new blood vessels number
Time frame: Day 14、Day 42
changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
Changes of local blood perfusion
Time frame: Day 60
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
5 secondary outcomes
Changes to the ABI from the baseline
Time frame: Day 60
Laser Speckle Imaging changes in blood flow from the baseline
Time frame: Day 60
Changes of pain score from the baseline
Time frame: Day 14、Day 28、Day 42、Day 60、Day 90
Gangrene /Ulcer changes from the baseline
Time frame: Day 14、Day 28、Day 42、Day 60、Day 90
Changes in quality of life scores from baseline
Time frame: Day 60
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Individual participant dataSharing planned: No
Related trials for Peripheral Artery Disease
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NL003 in people with Peripheral Artery Disease, run by Beijing Northland Biotech. Co., Ltd. at 1 site 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 15 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: status not confirmed, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yue Liu, MM (86-10-82890893, liuyue@northland-bio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of the new blood vessels number (time frame: Day 14、Day 42). 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?
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 1 Aug 2023.