A Phase 4 interventional study of Lower-Extremity Revascularization and Donaperminogene Seltoplasmid in Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer and Infrapopliteal Arterial Occlusive Disease, sponsored by First Affiliated Hospital of Wenzhou Medical University. Not yet recruiting at 6 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by First Affiliated Hospital of Wenzhou Medical University · Phase 4, Interventional, and Treatment
The goal of this clinical trial is to learn whether Seltoplasmid Injection can improve outcomes after lower-extremity revascularization. Revascularization is a procedure used to restore blood flow to the leg. The study will include adults with type 2 diabetes, a foot ulcer caused by poor blood flow, and disease mainly affecting the arteries below the knee.
The main questions are:
Participants in the Seltoplasmid group will receive injections into the muscles of the affected lower leg. The injections will be given on Day 0, Day 14, and Day 28.
Participants will be followed for 12 months. Researchers will also assess wound healing, survival without amputation, heart and blood vessel problems, pain, and blood flow in the affected leg.
Chronic limb-threatening ischemia in patients with diabetes is commonly associated with diffuse, calcified, and multilevel infrapopliteal arterial disease. In patients with ischemic diabetic foot ulcers, revascularization is recommended to restore blood flow, support wound healing, and reduce the risk of limb loss. However, restoration of patency in the main arteries does not always result in adequate perfusion of the distal tissue. Persistent microvascular dysfunction, impaired collateral formation, endothelial dysfunction, inflammation, infection, neuropathy, and abnormal wound-repair responses may continue after technically successful revascularization. Restenosis, repeat revascularization, delayed wound healing, major amputation, cardiovascular events, and death therefore remain important residual risks.
Seltoplasmid Injection is a plasmid-based gene therapy designed to produce local expression of two human hepatocyte growth factor isoforms. Hepatocyte growth factor activates c-Met-dependent signaling pathways involved in endothelial-cell survival, migration, angiogenesis, collateral-vessel development, microvascular repair, and tissue regeneration. Previous clinical studies in patients with severe lower-extremity ischemia have shown a potential benefit for ischemic ulcer healing. However, those studies primarily involved patients who were unsuitable for revascularization or in whom revascularization had produced an inadequate result.
Revascularization and Seltoplasmid Injection may have complementary biological effects. Revascularization restores blood flow and perfusion pressure through the main arterial pathway, whereas locally expressed hepatocyte growth factor may support distal collateral formation, microvascular perfusion, endothelial repair, and wound healing. This combined strategy is intended to address both macroscopic arterial obstruction and persistent impairment of distal tissue perfusion. Nevertheless, the clinical benefit and safety of administering Seltoplasmid Injection after revascularization have not been established in an adequately controlled randomized study.
This investigator-initiated trial is designed to evaluate the benefit-risk profile of this combined strategy in a high-risk population with diabetes, Rutherford category 5 chronic limb-threatening ischemia, ischemic foot ulceration, and predominantly infrapopliteal arterial disease. Randomization will occur only after completion of the index revascularization procedure and postoperative confirmation of eligibility and safety. This design ensures that treatment assignment cannot influence the revascularization procedure and excludes participants who cannot complete the procedure or do not meet the prespecified postoperative safety conditions.
The trial is open-label because the experimental group receives multiple intramuscular injections and the control group does not receive placebo injections. To reduce potential assessment bias, suspected primary endpoint events will be adjudicated by an independent clinical event committee whose members are blinded to treatment assignment. Standardized definitions will be used for major amputation, clinically driven target-limb revascularization, ulcer healing, cardiovascular events, and other clinical outcomes. Wound assessments and photographs, vascular examinations, and tissue-perfusion measurements will be performed using prespecified procedures whenever possible.
Seltoplasmid use after completed revascularization is outside its currently approved indication in China. Participants will be specifically informed of this off-label use, the uncertainty regarding additional benefit, the possibility of unknown risks, and the potential for increased injection-site bleeding or hematoma during antiplatelet or other antithrombotic treatment. Safety will be monitored throughout the study. An independent Data Monitoring Committee will periodically review accumulating safety information and may recommend continuation, modification, temporary suspension, or termination of the study in accordance with its charter.
The study is intended to determine whether adding Seltoplasmid Injection to contemporary revascularization and standardized background care can improve clinically meaningful limb and survival outcomes, wound healing, pain, and distal tissue perfusion without introducing unacceptable safety risks. The findings may provide evidence regarding a combined treatment strategy that targets both large-vessel blood flow and persistent microvascular impairment after infrapopliteal revascularization.
356 studies on the registry are indexed under Chronic Limb-Threatening Ischemia; 71 are open to participants now.
This study's planned enrollment of 180 is above the median of 40 across 239 interventional studies indexed under Chronic Limb-Threatening Ischemia.
Browse Chronic Limb-Threatening Ischemia studies →First Affiliated Hospital of Wenzhou Medical University is the lead sponsor of 83 studies on the registry; 57 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Following completion of the index lower-extremity revascularization procedure, participants will receive Seltoplasmid Injection in addition to protocol-defined standard care. Seltoplasmid will be administered at a total dose of 8 mg by intramuscular injection at 32 sites in the affected lower leg on Day 0, Day 14 (±3 days), and Day 28 (±3 days), provided that the prespecified safety conditions are met. Standard care includes wound care, offloading, glycemic control, treatment of infection, antiplatelet therapy, lipid-lowering therapy, and other clinically indicated treatment.
Procedure: Lower-Extremity Revascularization · Genetic: Donaperminogene Seltoplasmid
Following completion of the index lower-extremity revascularization procedure, participants will receive protocol-defined standard care without Seltoplasmid Injection or placebo injections. Standard care includes wound care, offloading, glycemic control, treatment of infection, antiplatelet therapy, lipid-lowering therapy, and other clinically indicated treatment. Participants will be followed according to the same visit schedule and outcome-assessment procedures as those in the experimental group.
Procedure: Lower-Extremity Revascularization
All participants will undergo index lower-extremity revascularization before randomization, with infrapopliteal arterial disease as the principal treatment target. The revascularization strategy and technique will be selected by the treating vascular specialist according to the participant's vascular anatomy, clinical condition, and protocol-defined procedural standards. After completion of the procedure and confirmation of postoperative eligibility and safety, participants will be randomized to one of the two study arms.
Seltoplasmid will be administered at a total dose of 8 mg per treatment session by intramuscular injection at 32 prespecified sites in the affected lower leg. Treatment will be administered on Day 0 after revascularization, Day 14 (±3 days), and Day 28 (±3 days), provided that the prespecified dosing and safety conditions are met.
Time to First Clinically Driven MALE or All-Cause Death
Time from randomization to the first occurrence of a clinically driven major adverse limb event (MALE) or all-cause death, whichever occurs first. MALE is defined as target-limb major amputation (amputation at or above the ankle) or clinically driven target-limb revascularization. Participants without an event will be censored at the date of their last available assessment. All suspected endpoint events will be adjudicated by an independent clinical event committee blinded to treatment assignment.
Time frame: From randomization through Day 360 (±14 days)
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Number and percentage of participants with treatment-emergent adverse events, serious adverse events, adverse reactions, adverse events leading to treatment discontinuation, and deaths. Events will be coded using MedDRA and graded according to the protocol-specified version of the Common Terminology Criteria for Adverse Events.
Time frame: From randomization through Day 360 (±14 days)
Incidence of Clinically Driven Target-Lesion Revascularization
Cumulative incidence of clinically driven target-lesion revascularization (CD-TLR) in the target limb. CD-TLR is defined as repeat endovascular or surgical treatment of the index target lesion prompted by recurrent or worsening clinical symptoms, wound deterioration, or objective evidence of impaired perfusion. Death and target-limb major amputation will be treated as competing events.
Time frame: From randomization through Day 360 (±14 days)
Amputation-Free Survival
Time from randomization to the first occurrence of target-limb major amputation or all-cause death, whichever occurs first. Major amputation is defined as amputation at or above the ankle. Participants without an event will be censored at the date of their last available assessment.
Time frame: From randomization through Day 360 (±14 days)
Proportion of Participants With Confirmed Complete Ulcer Healing
Proportion of participants with complete healing of the target ulcer, defined as complete epithelialization without drainage or the need for a dressing, confirmed at two consecutive scheduled assessments. Healing assessments will be supported by standardized wound measurement and photography.
Time frame: From randomization through Day 360 (±14 days)
Time to Confirmed Complete Ulcer Healing
Change from baseline in target-limb rest pain measured using an 11-point numerical rating scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. A decrease from baseline indicates improvement.
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Rest Pain Score
Change from baseline in target-limb rest pain measured using an 11-point numerical rating scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. A decrease from baseline indicates improvement.
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Transcutaneous Oxygen Pressure
Transcutaneous oxygen pressure (TcPO₂) will be measured in mmHg under standardized conditions at a prespecified, reproducible site near the target wound. The same device, probe location, participant position, and measurement conditions should be used whenever possible. An increase from baseline indicates improved tissue oxygenation and microcirculatory perfusion.
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Ankle-Brachial Index
Change from baseline in the ankle-brachial index (ABI) of the target limb at each scheduled assessment. ABI will be calculated as the higher target-ankle systolic pressure divided by the higher brachial systolic pressure, using a standardized measurement procedure. An increase from baseline generally indicates improved limb perfusion. ABI will be interpreted cautiously in participants with noncompressible arteries.
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Incidence of Major Adverse Cardiovascular Events
Cumulative incidence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Only the first qualifying event will be counted in the time-to-first-event analysis.
Time frame: From randomization through Day 360 (±14 days)
Plan to share: No — Individual participant data will not be made publicly available because the informed consent does not authorize unrestricted secondary use or public sharing of participant-level data. The dataset may contain sensitive clinical information, vascular imaging, wound photographs, and gene-therapy safety data. Aggregate and de-identified study results will be reported through trial registration, scientific publications, and other applicable regulatory channels.
Start is estimated for Oct 2026; primary completion for Oct 2028, 23 months later.
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This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Chronic Limb-Threatening Ischemia →
First Affiliated Hospital of Wenzhou Medical University