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Angiogenesis and Blood Perfusion Effect of HGF Gene Therapy in PAD Patients

Primary Purpose

Peripheral Artery Disease

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
NL003
Placebo
Sponsored by
Beijing Northland Biotech. Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Artery Disease focused on measuring Peripheral Artery Disease, Hepatocyte Growth Factor, NL003, Gene therapy, PET/CT-RGD, MIBI

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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; Exclusion Criteria: 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) 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.

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

investigational product

Placebo

Arm Description

Patients in this treatment group will receive 8mg NL003 respective in D0、14、28

Patients in this group will receive normal saline respective in D0、14、28

Outcomes

Primary Outcome Measures

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.
Changes of local blood perfusion
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.

Secondary Outcome Measures

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).
Laser Speckle Imaging changes in blood flow from the baseline
Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.
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
Gangrene /Ulcer changes from the baseline
Changes in the area of ulcer or gangrene from baseline after use of the study drug
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.

Full Information

First Posted
January 4, 2023
Last Updated
July 20, 2023
Sponsor
Beijing Northland Biotech. Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05968118
Brief Title
Angiogenesis and Blood Perfusion Effect of HGF Gene Therapy in PAD Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2022 (Actual)
Primary Completion Date
July 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Northland Biotech. Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Artery Disease
Keywords
Peripheral Artery Disease, Hepatocyte Growth Factor, NL003, Gene therapy, PET/CT-RGD, MIBI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
investigational product
Arm Type
Experimental
Arm Description
Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients in this group will receive normal saline respective in D0、14、28
Intervention Type
Drug
Intervention Name(s)
NL003
Other Intervention Name(s)
HGF plasmid, pCK-HGF-X7
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline
Intervention Description
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
Primary Outcome Measure Information:
Title
Changes of the new blood vessels number
Description
changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
Time Frame
Day 14、Day 42
Title
Changes of local blood perfusion
Description
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
Time Frame
Day 60
Secondary Outcome Measure Information:
Title
Changes to the ABI from the baseline
Description
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).
Time Frame
Day 60
Title
Laser Speckle Imaging changes in blood flow from the baseline
Description
Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.
Time Frame
Day 60
Title
Changes of pain score from the baseline
Description
The severity of critical Limb ischemia was assessed by Rutherford grading at screening、D14、D28、D42、D60、D90
Time Frame
Day 14、Day 28、Day 42、Day 60、Day 90
Title
Gangrene /Ulcer changes from the baseline
Description
Changes in the area of ulcer or gangrene from baseline after use of the study drug
Time Frame
Day 14、Day 28、Day 42、Day 60、Day 90
Title
Changes in quality of life scores from baseline
Description
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.
Time Frame
Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; Exclusion Criteria: 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) 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yue Liu, MM
Phone
86-10-82890893
Email
liuyue@northland-bio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yinjian Sun, MS
Phone
+86-10-82890893
Email
sunyinjian@northland-bio.com
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Changwei Liu
First Name & Middle Initial & Last Name & Degree
Xiao Di

12. IPD Sharing Statement

Plan to Share IPD
No

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Angiogenesis and Blood Perfusion Effect of HGF Gene Therapy in PAD Patients

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