Clinical trial NCT07023965: Follow-up Study Using Gene Therapy for Critical Limb Ischemia (NL003-CLI-III-L)
Official title: Multicenter Cohort Long-term Follow-up Study of Participants From Phase III Clinical Trials of Donaperminogene Seltoplasmid Injection for Critical Limb Ischemia
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
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
Lead sponsor: Beijing Northland Biotech. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-06-17
Enrollment: 542
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants were enrolled from the parent phase III clinical study identified by protocol numbers NCT04274049 and NCT04275323.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Incidence of benign and malignant tumors
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Incidence of significant vision loss, blindness, or other obvious visual abnormalities
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Incidence of major cardiovascular and cerebrovascular events
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Pregnancy status and its outcomes
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
Secondary outcomes:
measure: Amputation-free survival of the trial limb
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Amputation-free survival or target vessel revascularization composite endpoint
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Amputation-free survival or target vessel revascularization or neovascularization therapies (including stem cell or gene therapy) composite endpoint
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: All-cause mortality rate, time to death
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Major amputation rate of the trial limb (amputation plane above the ankle)
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Minor amputation rate of the trial limb (below the ankle, including toe amputation)
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Incidence of target vessel revascularization of the trial limb
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Rehospitalization rate for worsening ischemic symptoms of the trial limb
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Incidence of death due to acute myocardial infarction or stroke
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Time to amputation of the trial limb
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Level of amputation of the trial limb (above the knee, knee-ankle amputation, below the ankle amputation/toe amputation)
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Change in Rutherford classification of the trial limb compared to baseline at first dose
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Change in rest pain of the trial limb assessed by Numeric Rating Scale (NRS) compared to baseline at first dose
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
measure: Change in ulceration/necrosis of the trial limb compared to baseline at first dose
timeFrame: Every 3±1 months after enrollment, continuing until at least 36 months after the first dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
state: Neimenggu
city: Dalian
country: China
facility: zhongshan Hospital Affiliated of Dalian University
state: Shenyang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
Study officials:
References: