Follow-up Study Using Gene Therapy for Critical Limb Ischemia (NL003-CLI-III-L)

NCT07023965 | Enrolling By Invitation

• 1 other identifier: NL003-CLI-III-L
• Study Type: observational
• Target: 542
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this observational study is to learn about the long-term effects of Donaperminogene Seltoplasmid Injection (NL003) in participants who have been received drug NL003 or placebo at least one dose from the parent phase III clinical study to treat their critical limb ischemia (CLI). The main questions it aims to answer are:

• First, what medical problems do participants have after taking drug NL003 to treat CLI?
• Second, does drug NL003 make CLI participants live longer without serious problems (amputations or target vessel revascularizations) ? Participants who have already received drug NL003 for CLI will complete online surveys about their health conditions. This study will continue until at least 36 months after the participant's first dose.

Conditions

Peripheral Arterial Disease(PAD); Arterial Occlusive Disease; Arteriosclerosis Obliterans; Thromboangiitis Obliterans; Diabetic Foot Ulcer (DFU); Diabetic Foot Ulcer Ischemic; Critical Limb Ischemia (CLI)

Keywords

HGF; Critical Limb Ischemia; Gene therapy

Outcome Measures

Primary Outcomes (8)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Incidence of benign and malignant tumors

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Incidence of significant vision loss, blindness, or other obvious visual abnormalities

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Incidence of major cardiovascular and cerebrovascular events

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Pregnancy status and its outcomes

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Amputation-free survival of the trial limb

  Amputation-free survival of the trial limb is one of the key endpoints for efficacy assessment. The time from the first dose administration to the occurrence of amputation above the ankle of the trial limb or death due to any cause, whichever occurs first.

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Amputation-free survival or target vessel revascularization composite endpoint

  Amputation-free survival or target vessel revascularization composite endpoint is one of the key endpoints for efficacy assessment. The time from the first dose administration to the occurrence of amputation above the ankle of the trial limb, death due to any cause, or target vessel revascularization\* of the trial limb, whichever occurs first.\*Target vessel revascularization: bypass grafting, endovascular revascularization, thrombectomy, or thrombolysis of the trial limb.

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Amputation-free survival or target vessel revascularization or neovascularization therapies (including stem cell or gene therapy) composite endpoint

  Amputation-free survival or target vessel revascularization or neovascularization therapies (including stem cell or gene therapy) composite endpoint is one of the key endpoints for efficacy assessment. The time from the first dose administration to the occurrence of amputation above the ankle of the trial limb, death due to any cause, or target vessel revascularization and neovascularization therapies (including stem cell or gene therapy) of the trial limb, whichever occurs first.

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

Secondary Outcomes (11)

• All-cause mortality rate, time to death

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Major amputation rate of the trial limb (amputation plane above the ankle)

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Minor amputation rate of the trial limb (below the ankle, including toe amputation)

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Incidence of target vessel revascularization of the trial limb

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

• Rehospitalization rate for worsening ischemic symptoms of the trial limb

  Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

Study Arms (2)

Participants exposed to drug NL003 from Phase III Clinical Trials

Drug: NL003

Participants exposed to placebo from Phase III Clinical Trials

Drug: Placebo

Interventions

NL003 DRUG

This is an observational study, and the interventions have already been administered in the preceding Phase III clinical trials.

Participants exposed to drug NL003 from Phase III Clinical Trials

Placebo DRUG

This is an observational study, and the interventions have already been administered in the preceding Phase III clinical trials.

Participants exposed to placebo from Phase III Clinical Trials

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants were enrolled from the parent phase III clinical study identified by protocol numbers NCT04274049 and NCT04275323.

You may qualify if:

• Participants who have previously enrolled in Phase III clinical trials of recombinant human hepatocyte growth factor plasmid injection (Donaperminogene Seltoplasmid Injection) for the treatment of critical limb ischemia (including ulcers and rest pain) and have received at least one dose of the treatment.

You may not qualify if:

• Participants who refused to provide written informed consent;
• Participants who refused to cooperate with the retrospective or prospective data collection.

Sponsors & Collaborators

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

Study Sites (5)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100032, China

Location

Chifeng Municipal Hospital

Chifeng, Neimenggu, 024000, China

Location

zhongshan Hospital Affiliated of Dalian University

Dalian, Shenyang, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China

Location

The First Affiliated Hospital of Xi 'an Jiaotong University

Xi'an, China

Location

Related Links

• Related Info

MeSH Terms

Conditions

Peripheral Arterial Disease; Arterial Occlusive Diseases; Arteriosclerosis Obliterans; Thromboangiitis Obliterans; Diabetic Foot; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Vasculitis; Diabetic Angiopathies; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 17, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)