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

NCT04275323 | Completed Phase 3

• 1 other identifier: NL003-CLI-III-1
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 13

Brief 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)

Conditions

Arterial Occlusive Disease; Ischemia; Ulcers; Peripheral Vascular Disease

Keywords

HGF; Gene; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (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.

  Day180

Secondary Outcomes (9)

• The time when the pain completely goes away

  Day180

• Complete pain relief rate

  Day90

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

  Day14,Day28,Day60,Day90,Day120,Day180

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

  Day180

• The type and dose of analgesics varied from baseline

  Day14,Day28,Day60,Day90,Day120,Day180

Study Arms (2)

investigational produc

EXPERIMENTAL

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

Genetic: NL003

Placebo

PLACEBO COMPARATOR

Patients in this group will receive normal saline respective in D0、14、18

Other: Normal Saline

Interventions

NL003 GENETIC

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)

Also known as: HGF plasmid, pCK-HGF-X7

investigational produc

Normal Saline OTHER

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

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 20 and 80 (when signing informed consent), both male and female;
• \. 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;
• \. 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%.
• \. Agree to use appropriate contraceptive measures during the experiment;Female subjects of reproductive age, blood pregnancy test negative;
• \. Signed informed consent

You may not qualify if:

• \. Patients with acute lower limb ischemia or acute exacerbation of chronic lower limb ischemia.
• \. Vascular reconstruction (bypass or intravascular therapy) or sympathetic resection or amputation was performed within 4 weeks prior to the signing of the informed consent.
• \. 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.
• \. Main-iliac artery stenosis 70%.
• \. Patients with ischemic ulcer of lower extremity.
• \. NYHA classification of cardiac function is classified as grade (see annex 1 for specific classification criteria).
• \. Patients with unstable angina pectoris due to cerebral infarction, cerebral hemorrhage and myocardial infarction within 3 months before signing the informed consent.
• \. Refractory hypertension (taking three or more antihypertensive drugs, systolic blood pressure 180mmHg or diastolic blood pressure 110mmHg).
• \. Proliferative retinopathy and retinopathy examination is not available.
• \. Inability to accurately describe symptoms and emotions.
• \. Severe liver disease with uncompensated cirrhosis, jaundice, ascites or hemorrhagic varices.
• \. Current recipients of immunosuppressants or chemoradiotherapy.
• \. 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).
• \. 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.
• \. Patients with poor blood glucose control after treatment (hemoglobin a1c \>10%).

Sponsors & Collaborators

• Beijing Northland Biotech. Co., Ltd.: lead

Study Sites (13)

Beijing Hospitai

Beijing, Beijing Municipality, 100005, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

The Ninth People's Hospital of Chongqing

Chongqing, Chongqing Municipality, 400700, China

Location

Zhangzhou Municipal Hospital of Fujian Province

Zhangzhou, Fujian, 363000, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

Location

Xuzhou Mining Group General Hospital

Xuzhou, Jiangsu, 221006, China

Location

Chifeng Municipal Hospital

Chifeng, Neimenggu, 024000, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266003, China

Location

Shanghai seventh people's hospital

Shanghai, Shanghai Municipality, 200120, China

Location

Shanxi Provincial People's Hospital

Taiyuan, Shanxi, 030012, China

Location

First Affiliated Hospital of Xi 'an Jiaotong University

XiAn, Shanxi, 710061, China

Location

Second Affiliated Hospital of Xi 'an Jiaotong University

XiAn, Shanxi, 710061, China

Location

MeSH Terms

Conditions

Arterial Occlusive Diseases; Ischemia; Ulcer; Peripheral Vascular Diseases; Chronic Limb-Threatening Ischemia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2020
• First Posted: February 19, 2020
• Study Start: August 2, 2019
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: September 19, 2024

Record last verified: 2022-03

Locations

CN (13)