xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05968118</url>
    </required_header>
    <id_info>
      <org_study_id>NL003-PAD-III-3</org_study_id>
      <nct_id>NCT05968118</nct_id>
    </id_info>
    <brief_title>Angiogenesis and Blood Perfusion Effect of HGF Gene Therapy in PAD Patients</brief_title>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing Northland Biotech. Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Beijing Northland Biotech. Co., Ltd.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the&#xD;
        angiogenesis assessment of NL003 in PAD patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hepatocyte growth factor (HGF) gene therapy has been shown to be a potential choice for CLI&#xD;
        patients without surgical option. NL003, which is a DNA plasmid that contains novel genomic&#xD;
        cDNA hybrid human HGF coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and&#xD;
        HGF 723. Animal studies showed that NL003 inducing angiogenesis in the affected limb and&#xD;
        result in an increase in tissue perfusion. Our previous phase II clinical trial has suggested&#xD;
        the successful limb-salvaging capacity of NL003 in treatment of patients with CLTI.&#xD;
  &#xD;
        In this study we will use 68Ga RGD PET/CT and 99mTc MIBI SPECT imaging methods to evaluate&#xD;
        the effect of NL003 on angiogenesis and lower limb blood flow perfusion during the treatment&#xD;
        of chronic lower limb ischemia, and evaluated the effectiveness and safety of the drug. The&#xD;
        subjects will be randomly divided into the investigational drug group and the placebo group&#xD;
        in a 1:1 ratio. NL003 or placebo will be injected into the muscle of the affected limb on D0,&#xD;
        D14 and D28, 0.5mg/0.5mL/site, total 8mg, 32 sites. PET/CT will be measured on D14, D42&#xD;
        before drug administration, MIBI SPECT imaging will be collected on D60.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 29, 2022</start_date>
    <completion_date type="Anticipated">October 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Changes of the new blood vessels number</measure>
      <time_frame>Day 14、Day 42</time_frame>
      <description>changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of local blood perfusion</measure>
      <time_frame>Day 60</time_frame>
      <description>the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes to the ABI from the baseline</measure>
      <time_frame>Day 60</time_frame>
      <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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Laser Speckle Imaging changes in blood flow from the baseline</measure>
      <time_frame>Day 60</time_frame>
      <description>Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of pain score from the baseline</measure>
      <time_frame>Day 14、Day 28、Day 42、Day 60、Day 90</time_frame>
      <description>The severity of critical Limb ischemia was assessed by Rutherford grading at screening、D14、D28、D42、D60、D90</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gangrene /Ulcer changes from the baseline</measure>
      <time_frame>Day 14、Day 28、Day 42、Day 60、Day 90</time_frame>
      <description>Changes in the area of ulcer or gangrene from baseline after use of the study drug</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in quality of life scores from baseline</measure>
      <time_frame>Day 60</time_frame>
      <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.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Peripheral Artery Disease</condition>
    <arm_group>
      <arm_group_label>investigational product</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients in this treatment group will receive 8mg NL003 respective in D0、14、28</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Patients in this group will receive normal saline respective in D0、14、28</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NL003</intervention_name>
      <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)</description>
      <arm_group_label>investigational product</arm_group_label>
      <other_name>HGF plasmid</other_name>
      <other_name>pCK-HGF-X7</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <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</description>
      <arm_group_label>Placebo</arm_group_label>
      <other_name>Normal Saline</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. 18-80 years, diagnosed with chronic lower limb ischemia;&#xD;
  &#xD;
            2. According to DSA or CTA，severe stenosis (≥70%) or occlusion of one or more branches of&#xD;
               superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial&#xD;
               artery, and peroneal artery.&#xD;
  &#xD;
            3. Patients with obvious symptoms of lower limb ischemia, including severe claudication,&#xD;
               resting pain, ulcers, or gangrene.&#xD;
  &#xD;
            4. Agree to use appropriate contraceptive methods during the trial; Female subjects of&#xD;
               reproductive age, blood pregnancy test negative.&#xD;
  &#xD;
            5. Signing the informed consent.&#xD;
  &#xD;
            6. Can complete PETCT-RGD check and MIBI check;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. The foot or lower limb infection cannot be controlled, and amputation may be accepted&#xD;
               within 3 months.&#xD;
  &#xD;
            2. Those with cerebral infarction, cerebral hemorrhage, heart failure, unstable angina,&#xD;
               acute myocardial infarction, and serious arrhythmia within 3 months;&#xD;
  &#xD;
            3. Tumor patients diagnosed with malignant tumor or suspected of having malignant tumor&#xD;
               after tumor screening;&#xD;
  &#xD;
            4. Main iliac artery stenosis ≥ 70%;&#xD;
  &#xD;
            5. Refractory hypertension (taking three or more antihypertensive drugs, systolic blood&#xD;
               pressure ≥ 180mmHg or diastolic blood pressure ≥ 110mmHg);&#xD;
  &#xD;
            6. Anti HIV antibody positive person, anti hepatitis C antibody positive person and RNA&#xD;
               positive person, hepatitis B surface antigen positive person (if the subject is HBsAg&#xD;
               positive, and judging by peripheral blood HBV DNA, the researcher believes that the&#xD;
               subject is in a stable period of chronic hepatitis B, which will not increase the risk&#xD;
               of the subject, the subject can be selected)&#xD;
  &#xD;
            7. Patients with poor blood glucose control after treatment (HbA1c&gt;10%);&#xD;
  &#xD;
            8. Persons allergic to contrast medium&#xD;
  &#xD;
            9. The investigator believes that the patient's complications affect the evaluation of&#xD;
               safety and effectiveness, or the expected survival period is less than 12 months;&#xD;
  &#xD;
           10. Those who regularly drink more than 14 units of alcohol (1 unit=360 mL beer or 45 mL&#xD;
               liquor or 150 mL wine with 40% alcohol) or drug abusers within 12 months before&#xD;
               signing the informed consent form;&#xD;
  &#xD;
           11. Acute lower limb ischemia or acute aggravation of chronic lower limb ischemia;&#xD;
  &#xD;
           12. Those who received vascular reconstruction of the affected limb within 4 weeks before&#xD;
               the informed consent form and whose blood supply improved after the operation&#xD;
  &#xD;
           13. Serious liver or kidney disease or severe anemia judged by the investigator;&#xD;
  &#xD;
           14. Those who cannot correctly describe symptoms and emotions;&#xD;
  &#xD;
           15. Those who participated in other clinical trials within 3 months before signing the&#xD;
               informed consent form.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Yue Liu, MM</last_name>
      <phone>86-10-82890893</phone>
      <email>liuyue@northland-bio.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Yinjian Sun, MS</last_name>
      <phone>+86-10-82890893</phone>
      <email>sunyinjian@northland-bio.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Peking Union Medical College Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100032</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <investigator>
        <last_name>Changwei Liu</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Xiao Di</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>January 4, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Peripheral Artery Disease</keyword>
    <keyword>Hepatocyte Growth Factor</keyword>
    <keyword>NL003</keyword>
    <keyword>Gene therapy</keyword>
    <keyword>PET/CT-RGD</keyword>
    <keyword>MIBI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Arterial Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05968118
  org study id: NL003-PAD-III-3
  nct id: NCT05968118
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Changes of the new blood vessels number
  time frame: Day 14、Day 42
  description: changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
  measure: Changes of local blood perfusion
  time frame: Day 60
  description: the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
  measure: Changes to the ABI from the baseline
  time frame: Day 60
  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).
  measure: Laser Speckle Imaging changes in blood flow from the baseline
  time frame: Day 60
  description: Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.
  measure: Changes of pain score from the baseline
  time frame: Day 14、Day 28、Day 42、Day 60、Day 90
  description: The severity of critical Limb ischemia was assessed by Rutherford grading at screening、D14、D28、D42、D60、D90
  measure: Gangrene /Ulcer changes from the baseline
  time frame: Day 14、Day 28、Day 42、Day 60、Day 90
  description: Changes in the area of ulcer or gangrene from baseline after use of the study drug
  measure: Changes in quality of life scores from baseline
  time frame: Day 60
  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.
  arm group label: investigational product
  arm group type: Experimental
  description: Patients in this treatment group will receive 8mg NL003 respective in D0、14、28
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Patients in this group will receive normal saline respective in D0、14、28
  intervention type: Drug
  intervention name: NL003
  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)
  arm group label: investigational product
  other name: HGF plasmid
  other name: pCK-HGF-X7
  intervention type: Drug
  intervention name: Placebo
  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
  arm group label: Placebo
  other name: Normal Saline
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Yue Liu, MM
  phone: 86-10-82890893
  email: liuyue@northland-bio.com
  last name: Yinjian Sun, MS
  phone: +86-10-82890893
  email: sunyinjian@northland-bio.com
  facility: 
  status: Recruiting
  investigator: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Peripheral Arterial Disease
  sharing ipd: No