Arterial Occlusive Disease, Arteriosclerosis Obliterans, Critical Limb Ischemia (CLI), Diabetic Foot Ulcer (DFU), Diabetic Foot Ulcer Ischemic, Peripheral Arterial Disease(PAD), Thromboangiitis Obliterans
Conditions
Keywords
HGF, Critical Limb Ischemia, Gene therapy
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.
Interventions
DRUGNL003
This is an observational study, and the interventions have already been administered in the preceding Phase III clinical trials.
DRUGPlacebo
This is an observational study, and the interventions have already been administered in the preceding Phase III clinical trials.
Sponsors
Beijing Northland Biotech. Co., Ltd.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| All-cause mortality rate, time to death | Every 3±1 months after enrollment, continuing until at least 36 months after the first dose | — |
| 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 | — |
| 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. |
| 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 | — |
| 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 | — |
| 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 | — |
Countries
China
Outcome results
None listed