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

• Conditions: Peripheral Arterial Disease(PAD); Arterial Occlusive Disease; Arteriosclerosis Obliterans; Thromboangiitis Obliterans; Diabetic Foot Ulcer (DFU); Diabetic Foot Ulcer Ischemic; Critical Limb Ischemia (CLI)
• Interventions: Drug: NL003; Drug: Placebo

• Registration Number: NCT07023965
• Lead Sponsor: Beijing Northland Biotech. Co., Ltd.

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.

Detailed Description

This study is a multicenter, open-label, long-term follow-up cohort study. A remote follow-up system is recommended as a tool for the study, however, in-person visits or phone calls at the research center will be conducted if remote follow-up is not feasible. The study will retrospectively collect data from the last visit in the parent Phase III study and prospectively gather data following informed consent. It will continue until at least 36 months after the first dose administered to the last enrolled participant.

Study Timeline

• Study First Submitted: 2025-06-06
• Study First Submitted QC: 2025-06-15
• Study First Posted: 2025-06-17
• Study Start: 2025-06-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-11
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 542

Inclusion Criteria

• 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.

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants exposed to drug NL003 from Phase III Clinical Trials	NL003	-
Participants exposed to placebo from Phase III Clinical Trials	Placebo	-

Primary Outcome Measures

Name	Time	Method
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
Amputation-free survival or target vessel revascularization or neovascularization therapies (including stem cell or gene therapy) composite endpoint	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 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.
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 or target vessel revascularization composite endpoint	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 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.
Amputation-free survival of the trial limb	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose	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.

Secondary Outcome Measures

Name	Time	Method
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
Incidence of death due to acute myocardial infarction or stroke	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
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
Time to amputation of the trial limb	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
Level of amputation of the trial limb (above the knee, knee-ankle amputation, below the ankle amputation/toe amputation)	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
Change in Rutherford classification of the trial limb compared to baseline at first dose	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose	The Rutherford classification is a standardized system used to assess the severity of peripheral arterial disease (PAD) in the trial limb. It ranges from category 0 (asymptomatic) to category 6 (ischemic rest pain with gangrene). Higher categories indicate more severe disease. The change in Rutherford classification will be measured by comparing the classification at the first dose to the baseline classification.
Change in rest pain of the trial limb assessed by Numeric Rating Scale (NRS) compared to baseline at first dose	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose	The NRS is a pain assessment tool that ranges from 0 to 10, where 0 indicates no pain and 10 indicates the worst possible pain. A higher score on the NRS indicates worse pain. The change in rest pain will be determined by comparing the NRS score at the first dose to the baseline NRS score.
Change in ulceration/necrosis of the trial limb compared to baseline at first dose	Every 3±1 months after enrollment, continuing until at least 36 months after the first dose

Trial Locations

Locations (5)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Chifeng Municipal Hospital; 🇨🇳 Chifeng, Neimenggu, China

zhongshan Hospital Affiliated of Dalian University; 🇨🇳 Dalian, Shenyang, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, China

The First Affiliated Hospital of Xi 'an Jiaotong University; 🇨🇳 Xi'an, China