Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia (NL003-CLI-III-2)

NCT04274049 | Completed Phase 3

• 2 other identifiers: NL003-CLI-III-2CTR20190750
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this study is to evaluate whether intramuscular injections of NL003 into the calf is safe and effective in the treatment of critical limb ischemia

Conditions

Arterial Occlusive Disease; Ischemia; Ulcers; Peripheral Vascular Disease

Keywords

HGF; Gene; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (1)

• Percentage of ulcer complete healing

  1.At D180 visit, subjects intended to observe the healing of all arterial ischemic ulcers in the limb;2.Ulcer healing criteria: skin epidermal cell regeneration without secretion.

  Day180

Secondary Outcomes (10)

• The time when the ulcer finally heals completely

  Day14,Day28,Day60,Day90,Day120,Day180

• Percentage of cases with ulcer area reduced by ≥50% from baseline

  Day180

• Percentage of new ulcer or gangrene cases

  Day14,Day28,Day60,Day90,Day120,Day180

• Rate of complete disappearance of pain

  Day180

• Percentage of cases with a 50% reduction in pain score from baseline

  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:

• \. At the age of 20 and 80 (at the time of signing the informed consent), both male and female.
• \. Patients with chronic lower limb arterial ischemia complicated with ulceration also met the following requirements: when signing the informed consent, the ischemic ulcer of the artery lasted at least 2 weeks;When signing the informed consent, the area of a single ulcer is no more than 10cm2;If there are multiple ulcers in the affected limb selected at the time of signing the informed consent, the total number of ulcers shall not exceed 3.Basic ulcer care (according to standard ulcer care procedure) should be maintained during the test to avoid aggravation of infection.The ulcer did not expose bone or joint capsule.If there is gangrene, only partial toe gangrene.
• \. Agreed to use the basic treatment drugs as required during the test, and kept a complete record of the subjects' diaries on time. The compliance of the basic treatment drugs and the subjects' diaries 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 the surgical operation, the patient was still in the postoperative risk period, and the researcher judged that it was not suitable for the participant.
• \. Main-iliac artery stenosis ≥70%.
• \. Severe limb infection (cellulitis, osteomyelitis, etc.), distal fascia or bone exposure were observed.
• \. Cardiac function NYHA class belongs to Ⅳ grading standards (see appendix 1).
• \. Cerebral infarction, cerebral hemorrhage, myocardial infarction or unstable angina pectoris occurred within 3 months before signing the informed consent.
• \. Refractory hypertension (systolic blood pressure ≥180mmHg or diastolic blood pressure ≥110mmHg when taking three or more antihypertensive drugs).
• \. 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 \< 3.0×109/L, platelet \< 75×109/L, upper limit of normal AST or ALT \>, upper limit of normal serum creatinine \> was 3 times, or other laboratory examination indicators showed abnormalities that researchers thought might affect the evaluation of test results.
• \. Poor blood glucose control after treatment (glycosylated hemoglobin \> 10%).

Sponsors & Collaborators

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

Study Sites (21)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Location

Zhongshan Hospital Xiamen University

Xiamen, Fujian, China

Location

Zhangzhou Municipal Hospital of Fujian Province

Zhangzhou, Fujian, 363000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 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

The First Affiliated Hospital of Zhengzhou University

Changchun, Jilin, China

Location

Affiliated Hospital of Inner Mongolia Medical University

Baotou, Neimenggu, China

Location

Chifeng Municipal Hospital

Chifeng, Neimenggu, 024000, China

Location

Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Jinan, Shandong, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266003, China

Location

Qingdao Hiser Hospital Affiliated of Qingdao University（Qingdao Traditional Chinese Medicine Hospital）

Qingdao, Shandong, China

Location

Fudan University Affiliated Pudong Medical Center

Shanghai, Shanghai Municipality, China

Location

Shanghai 9th People's Hospital Affiliated to Shanghai JiaoTong University, School of Medicine;

Shanghai, Shanghai Municipality, 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

The First Affiliated Hospital，Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Location

zhongshan Hospital Affiliated of Dalian University

Dalian, 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 Officials

• Changwei Liu, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

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 18, 2020
• Study Start: August 28, 2019
• Primary Completion: December 23, 2023
• Study Completion: December 23, 2023
• Last Updated: September 20, 2024

Record last verified: 2024-09

Locations

CN (21)