Chronic Limb-Threatening IschemiaPhase 4NCT07827521

Seltoplasmid Plus Revascularization for Diabetic Infrapopliteal Chronic Limb-Threatening Ischemia

A Phase 4 study testing Lower-Extremity Revascularization and Donaperminogene Seltoplasmid in people with Chronic Limb-Threatening Ischemia and Diabetic Foot Ulcer, run by First Affiliated Hospital of Wenzhou Medical University at 6 sites in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer, Infrapopliteal Arterial Occlusive Disease
What is being tested?: Lower-Extremity Revascularization and Donaperminogene Seltoplasmid
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 180 participants
Where: 6 sitesChina
Study dates: 20 Oct 2026to 31 Dec 2029
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, aged 18 years or older at the time of signing informed consent
Clinical diagnosis of type 2 diabetes mellitus with a diabetic foot ulcer and chronic limb-threatening ischemia classified as Rutherford category 5. The target limb must have an ischemic foot ulcer corresponding to WIfI wound grade 1 or 2. After at least 2 weeks of optimal standard wound care, including debridement, offloading, and infection control as clinically indicated, the ulcer must show no clear healing tendency, defined as a reduction in area of less than 30%, and infrapopliteal revascularization must be considered necessary to improve perfusion and promote wound healing.
Color duplex ultrasonography, computed tomography angiography (CTA), or digital subtraction angiography (DSA) demonstrates at least 70% stenosis or occlusion in one or more infrapopliteal arteries, the anterior tibial, posterior tibial, or peroneal artery, and the investigator considers this disease to be the principal cause of ischemia in the target limb.
No severe stenosis in the supra-popliteal inflow arteries, including the iliac, femoral, and popliteal arteries, defined as less than 70% stenosis; alternatively, any severe inflow stenosis can be treated during the index procedure. The infrapopliteal lesion or lesions must remain the principal revascularization target.
Objective evidence of severe limb ischemia meeting at least one of the following criteria: ankle-brachial index (ABI) ≤0.50; ankle systolic pressure measured at the dorsalis pedis or posterior tibial artery ≤70 mmHg; or transcutaneous oxygen pressure (TcPO₂) <30 mmHg. If ABI is >1.30 or otherwise considered unreliable because of arterial incompressibility, eligibility will be determined using toe-brachial index (TBI), toe pressure where available, and/or TcPO₂.
Willing and able to comply with study procedures and complete all scheduled follow-up assessments.
Provides written informed consent voluntarily before any study-specific procedure.

Who cannot join

Unable or unwilling to undergo lower-extremity arterial revascularization.
WIfI foot-infection grade 3, including systemic infection or severe local infection requiring urgent surgical debridement. A potential participant may be reassessed after adequate antimicrobial and surgical management if the infection has improved to WIfI infection grade 1 or 2, systemic infection has resolved, and relevant infection indicators have returned to an acceptable range.
Gangrene or tissue destruction of the target limb for which above-ankle major amputation is considered immediately necessary or unavoidable.
Any contraindication to seltoplasmid injection according to the current prescribing information.
Acute myocardial infarction, stroke, intracranial hemorrhage, or unstable angina within 3 months before randomization.
Acute limb ischemia or acute exacerbation of chronic limb ischemia within 3 months before randomization.

Show all 21Show fewer

New York Heart Association class IV heart failure.
Severe hepatic impairment, including decompensated cirrhosis, jaundice, ascites, or variceal bleeding.
Severe renal impairment, defined as serum creatinine >2.5 times the upper limit of normal or estimated glomerular filtration rate <30 mL/min/1.73 m², or current dialysis.
Coagulation disorder, defined as platelet count <75 × 10⁹/L or international normalized ratio >1.5 that cannot be corrected.
Hemoglobin <80 g/L or white blood cell count <3.0 × 10⁹/L.
Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal.
Poorly controlled diabetes mellitus, defined as glycated hemoglobin >10%.
Active malignant tumor or a history of malignant tumor within 5 years before enrollment. Any broader malignancy-related contraindication in the current seltoplasmid prescribing information will take precedence.
Pregnant or breastfeeding woman, or woman of childbearing potential unwilling to use effective contraception during the protocol-defined period. Pregnancy testing and contraceptive requirements will follow the protocol and current prescribing information.
Life expectancy <12 months or, in the investigator's judgment, inability to complete follow-up.
Participation in another interventional clinical study within 30 days before enrollment.
Positive human immunodeficiency virus antibody; positive hepatitis C virus antibody; or positive hepatitis B surface antigen together with detectable peripheral-blood hepatitis B virus DNA when, in the investigator's judgment, active chronic hepatitis B may increase participant risk.
Current treatment with immunosuppressive therapy, radiotherapy, or chemotherapy.
Any serious comorbidity that may interfere with assessment of study outcomes, or any psychological or social circumstance that may materially prevent optimal participation in the study, in the investigator's judgment.
Any other condition that, in the investigator's judgment and with the reason documented, makes participation inappropriate or exposes the participant to unacceptable risk.

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jingyong Huang contact

Xiang Su contact

City, postcode or hospital

6 sites in 1 country

China6 sites

The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejing, 310003
Hongkun Zhang, M.D., Ph.D., +86-571-87236745, doczhk@163.com
Hangzhou First People's Hospital
Hangzhou, Zhejing, 310006
Xin Fang, M.D., Ph.D., +86-571-56007032, hzsyyy1@163.com
Zhejiang Provincial People's Hospital
Hangzhou, Zhejing, 310014
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejing, 310016
Jing Yang, M.D., Ph.D., 86-571-86090073, Yangjinsir@163.com
Taizhou Hospital of Zhejiang Province
Taizhou, Zhejing, 317000
Wenjun Zhao, M.D., Ph.D., +86-139-5856-1810, zhaowj@enzemed.com
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejing, 325000
Jingyong Huang, M.D., +8613616631391, 43737136@qq.com

Other trials in China

About this study

Official title: A Multicenter, Randomized, Open-Label, Controlled Trial to Evaluate the Safety and Efficacy of Seltoplasmid Injection Combined With Revascularization for Chronic Limb-Threatening Ischemia Caused by Infrapopliteal Artery Disease in Patients With Diabetes

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:

Does adding Seltoplasmid lower the risk of major amputation, another procedure to restore blood flow, or death?
What medical problems occur after treatment with Seltoplasmid? About 180 participants will undergo standard lower-extremity revascularization. After the procedure, eligible participants will be assigned by chance to one of two groups. One group will receive Seltoplasmid plus standard care. The other group will receive standard care alone.

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.

Read the detailed description

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.

Conditions: Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer, Infrapopliteal Arterial Occlusive Disease
Being tested: Lower-Extremity Revascularization, Donaperminogene Seltoplasmid
Keywords: Seltoplasmid, Revascularization, Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer, infrapopliteal arterial occlusive disease
Medical subject headings: Chronic Limb-Threatening Ischemia, Diabetic Foot

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Lower-Extremity RevascularizationProcedure or surgery
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.
Donaperminogene SeltoplasmidGenetic
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.

Study groups in NCT07827521
Study group	Role	What they receive
Seltoplasmid Plus Revascularization	Experimental	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. Receives: Procedure: Lower-Extremity Revascularization; Genetic: Donaperminogene Seltoplasmid
Revascularization	Active comparator	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. Receives: Procedure: Lower-Extremity Revascularization

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: From randomization through Day 360 (±14 days)

Secondary outcomes (9)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From randomization through Day 360 (±14 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Oct 202631 Dec 2029

First posted18 Sep 2026
Study start20 Oct 2026 (estimated)
Primary completion1 Oct 2028 (estimated)
Study completion31 Dec 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (52)Papers the sponsor has linked to this study.
Other trials for Chronic Limb-Threatening IschemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Multicenter, randomized, open-label, two-arm, parallel-group, controlled superiority study. After completion of the index lower-extremity revascularization procedure and confirmation of postoperative eligibility and safety, participants will be randomized in a 1:1 ratio to receive either Seltoplasmid Injection plus standard care or standard care alone. Participants will remain in their assigned groups and will be followed for 12 months.
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 180 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07827521
Sponsor's protocol ID: ky2026-432
Status last verified: Sep 2026
First submitted: 11 Sep 2026
Last updated: 18 Sep 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: 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.

Publications

Weissler EH, Wang Y, Gales JM, Feldman DN, Arya S, Secemsky EA, Aronow HD, Hawkins BM, Gutierrez JA, Patel MR, Curtis JP, Jones WS, Swaminathan RV. Cardiovascular and Limb Events Following Endovascular Revascularization Among Patients >/=65 Years Old: An American College of Cardiology PVI Registry Analysis. J Am Heart Assoc. 2022 Jun 21;11(12):e024279. doi: 10.1161/JAHA.121.024279. Epub 2022 Jun 20.
PubMed 35723018
Conte MS, Azene E, Doros G, Gasper WJ, Hamza T, Kashyap VS, Guzman R, Mena-Hurtado C, Menard MT, Rosenfield K, Rowe VL, Strong M, Farber A. Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial. J Vasc Surg. 2024 Jun;79(6):1428-1437.e4. doi: 10.1016/j.jvs.2024.02.005. Epub 2024 Feb 17.
PubMed 38368997
Gu Y, Cui S, Yu T, Liao L, Guo J. Nine-year follow-up of patients receiving recombinant human hepatocyte growth factor nude plasmid DNA for critical limb ischemia: updated safety and efficacy results. 2024.
Di X, Liu C, Ni L, Ye W, Rong Z, Zhang R, Niu S, Li F, Zheng Y, Han C, Liu Y. Rationale and design for the study of recombinant human hepatocyte growth factor plasmid in the treatment of patients with chronic limb-threatening ischemia (HOPE CLTI): Randomized, placebo-controlled, double-blind, phase III clinical trials. Am Heart J. 2022 Dec;254:88-101. doi: 10.1016/j.ahj.2022.08.007. Epub 2022 Aug 21.
PubMed 36002048
Di X, Wang P, Li F, Han W, Ni L, Liu CW. Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. 2024 Nov;68(5):619-628. doi: 10.1016/j.ejvs.2024.07.016. Epub 2024 Jul 15.
PubMed 39019317
Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30. doi: 10.1016/j.jvs.2010.07.044.
PubMed 21146749
Shigematsu H, Yasuda K, Iwai T, Sasajima T, Ishimaru S, Ohashi Y, Yamaguchi T, Ogihara T, Morishita R. Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia. Gene Ther. 2010 Sep;17(9):1152-61. doi: 10.1038/gt.2010.51. Epub 2010 Apr 15.
PubMed 20393508
Di X, Liu C, Sun S, Qin J, Guo X, Chen Y, Li X, Zhang H, Liu M, Yang L, Zhao H, Lu S, Huang J, Zhang Y, Li J, Lin X, Yao K, Tang J, Wang J, Gao Z, Wang J, Huang X, Xu S, Liu Y, Han W, Ni L, Ye W, Zheng Y, Chen Y, Liu B. Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial. Mol Ther. 2025 Jul 2;33(7):3423-3433. doi: 10.1016/j.ymthe.2025.04.009. Epub 2025 Apr 11.
PubMed 40221835
Gu Y, Cui S, Wang Q, Liu C, Jin B, Guo W, Liu C, Chu T, Shu C, Zhang F, Han C, Liu Y. A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. Mol Ther. 2019 Dec 4;27(12):2158-2165. doi: 10.1016/j.ymthe.2019.10.017. Epub 2019 Oct 31.
PubMed 31805256
Hahn W, Pyun WB, Kim DS, Yoo WS, Lee SD, Won JH, Shin GJ, Kim JM, Kim S. Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model. J Gene Med. 2011 Oct;13(10):549-55. doi: 10.1002/jgm.1603.
PubMed 21898720
Pyun WB, Hahn W, Kim DS, Yoo WS, Lee SD, Won JH, Rho BS, Park ZY, Kim JM, Kim S. Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia. Gene Ther. 2010 Dec;17(12):1442-52. doi: 10.1038/gt.2010.101. Epub 2010 Jul 29.
PubMed 20668482
Zhao J, Wang W, Ha CH, Kim JY, Wong C, Redmond EM, Hamik A, Jain MK, Feng GS, Jin ZG. Endothelial Grb2-associated binder 1 is crucial for postnatal angiogenesis. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1016-23. doi: 10.1161/ATVBAHA.111.224493. Epub 2011 Mar 3.
PubMed 21372298
Jin ZG, Ueba H, Tanimoto T, Lungu AO, Frame MD, Berk BC. Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ Res. 2003 Aug 22;93(4):354-63. doi: 10.1161/01.RES.0000089257.94002.96. Epub 2003 Jul 31.
PubMed 12893742
Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature. 2005 Sep 15;437(7057):426-31. doi: 10.1038/nature03952.
PubMed 16163360
Hammad TA, Rundback J, Bunte M, Miller L, Patel PD, Sadanandan S, Fitzgerald M, Pastore J, Kashyap V, Henry TD, Shishehbor MH. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results. J Endovasc Ther. 2020 Aug;27(4):669-675. doi: 10.1177/1526602820919951. Epub 2020 May 18.
PubMed 32419594

Interested in taking part?

Jingyong Huang

+8613600672565

43737136@qq.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Open-Label, Controlled Trial to Evaluate the Safety and Efficacy of Seltoplasmid Injection Combined With Revascularization for Chronic Limb-Threatening Ischemia Caused by Infrapopliteal Artery Disease in Patients With Diabetes
ClinicalTrials.gov ID: NCT07827521
Acronym / sponsor ID: ky2026-432
Conditions: Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer, Infrapopliteal Arterial Occlusive Disease
Keywords: Seltoplasmid, Revascularization, Chronic Limb-Threatening Ischemia, Diabetic Foot Ulcer, infrapopliteal arterial occlusive disease
Phase: Phase 4
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 180 participants (estimated)
Lead sponsor: First Affiliated Hospital of Wenzhou Medical UniversityUniversity, hospital or other
Collaborators: Beijing Northland Biotech. Co., Ltd.
Study start: 20 Oct 2026 (estimated)
Primary completion: 1 Oct 2028 (estimated)
Study completion: 31 Dec 2029 (estimated)
First posted: 18 Sep 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The main questions are:

Does adding Seltoplasmid lower the risk of major amputation, another procedure to restore blood flow, or death?
What medical problems occur after treatment with Seltoplasmid? About 180 participants will undergo standard lower-extremity revascularization. After the procedure, eligible participants will be assigned by chance to one of two groups. One group will receive Seltoplasmid plus standard care. The other group will receive standard care alone.

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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: Multicenter, randomized, open-label, two-arm, parallel-group, controlled superiority study. After completion of the index lower-extremity revascularization procedure and confirmation of postoperative eligibility and safety, participants will be randomized in a 1:1 ratio to receive either Seltoplasmid Injection plus standard care or standard care alone. Participants will remain in their assigned groups and will be followed for 12 months.

Arm	Type	Receives
Seltoplasmid Plus Revascularization	Experimental	Procedure: Lower-Extremity Revascularization, Genetic: Donaperminogene SeltoplasmidFollowing 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.
Revascularization	Active comparator	Procedure: Lower-Extremity RevascularizationFollowing 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female, aged 18 years or older at the time of signing informed consent
Clinical diagnosis of type 2 diabetes mellitus with a diabetic foot ulcer and chronic limb-threatening ischemia classified as Rutherford category 5. The target limb must have an ischemic foot ulcer corresponding to WIfI wound grade 1 or 2. After at least 2 weeks of optimal standard wound care, including debridement, offloading, and infection control as clinically indicated, the ulcer must show no clear healing tendency, defined as a reduction in area of less than 30%, and infrapopliteal revascularization must be considered necessary to improve perfusion and promote wound healing.
Color duplex ultrasonography, computed tomography angiography (CTA), or digital subtraction angiography (DSA) demonstrates at least 70% stenosis or occlusion in one or more infrapopliteal arteries, the anterior tibial, posterior tibial, or peroneal artery, and the investigator considers this disease to be the principal cause of ischemia in the target limb.
No severe stenosis in the supra-popliteal inflow arteries, including the iliac, femoral, and popliteal arteries, defined as less than 70% stenosis; alternatively, any severe inflow stenosis can be treated during the index procedure. The infrapopliteal lesion or lesions must remain the principal revascularization target.
Objective evidence of severe limb ischemia meeting at least one of the following criteria: ankle-brachial index (ABI) ≤0.50; ankle systolic pressure measured at the dorsalis pedis or posterior tibial artery ≤70 mmHg; or transcutaneous oxygen pressure (TcPO₂) <30 mmHg. If ABI is >1.30 or otherwise considered unreliable because of arterial incompressibility, eligibility will be determined using toe-brachial index (TBI), toe pressure where available, and/or TcPO₂.

Key exclusion criteria (21 listed)

Unable or unwilling to undergo lower-extremity arterial revascularization.
WIfI foot-infection grade 3, including systemic infection or severe local infection requiring urgent surgical debridement. A potential participant may be reassessed after adequate antimicrobial and surgical management if the infection has improved to WIfI infection grade 1 or 2, systemic infection has resolved, and relevant infection indicators have returned to an acceptable range.
Gangrene or tissue destruction of the target limb for which above-ankle major amputation is considered immediately necessary or unavoidable.
Any contraindication to seltoplasmid injection according to the current prescribing information.
Acute myocardial infarction, stroke, intracranial hemorrhage, or unstable angina within 3 months before randomization.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Lower-Extremity RevascularizationAll 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.	Procedure or surgery	Revascularization, Seltoplasmid Plus Revascularization
Donaperminogene SeltoplasmidSeltoplasmid 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.	Genetic	Seltoplasmid Plus Revascularization

Primary outcome

Time to First Clinically Driven MALE or All-Cause Death
Time frame: From randomization through Day 360 (±14 days)
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.

9 secondary outcomes

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Time frame: From randomization through Day 360 (±14 days)
Incidence of Clinically Driven Target-Lesion Revascularization
Time frame: From randomization through Day 360 (±14 days)
Amputation-Free Survival
Time frame: From randomization through Day 360 (±14 days)
Proportion of Participants With Confirmed Complete Ulcer Healing
Time frame: From randomization through Day 360 (±14 days)
Time to Confirmed Complete Ulcer Healing
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Rest Pain Score
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Transcutaneous Oxygen Pressure
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Change From Baseline in Target-Limb Ankle-Brachial Index
Time frame: Baseline and scheduled assessments through Day 360 (±14 days)
Incidence of Major Adverse Cardiovascular Events
Time frame: From randomization through Day 360 (±14 days)

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
Background: PubMed 35723018Weissler EH, Wang Y, Gales JM, Feldman DN, Arya S, Secemsky EA, Aronow HD, Hawkins BM, Gutierrez JA, Patel MR, Curtis JP, Jones WS, Swaminathan RV. Cardiovascular and Limb Events Following Endovascular Revascularization Among Patients >/=65 Years Old: An American College of Cardiology PVI Registry Analysis. J Am Heart Assoc. 2022 Jun 21;11(12):e024279. doi: 10.1161/JAHA.121.024279. Epub 2022 Jun 20.
Results publication: PubMed 38368997Conte MS, Azene E, Doros G, Gasper WJ, Hamza T, Kashyap VS, Guzman R, Mena-Hurtado C, Menard MT, Rosenfield K, Rowe VL, Strong M, Farber A. Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial. J Vasc Surg. 2024 Jun;79(6):1428-1437.e4. doi: 10.1016/j.jvs.2024.02.005. Epub 2024 Feb 17.
Results publicationGu Y, Cui S, Yu T, Liao L, Guo J. Nine-year follow-up of patients receiving recombinant human hepatocyte growth factor nude plasmid DNA for critical limb ischemia: updated safety and efficacy results. 2024.
Results publication: PubMed 36002048Di X, Liu C, Ni L, Ye W, Rong Z, Zhang R, Niu S, Li F, Zheng Y, Han C, Liu Y. Rationale and design for the study of recombinant human hepatocyte growth factor plasmid in the treatment of patients with chronic limb-threatening ischemia (HOPE CLTI): Randomized, placebo-controlled, double-blind, phase III clinical trials. Am Heart J. 2022 Dec;254:88-101. doi: 10.1016/j.ahj.2022.08.007. Epub 2022 Aug 21.
Results publication: PubMed 39019317Di X, Wang P, Li F, Han W, Ni L, Liu CW. Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. 2024 Nov;68(5):619-628. doi: 10.1016/j.ejvs.2024.07.016. Epub 2024 Jul 15.
Results publication: PubMed 21146749Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30. doi: 10.1016/j.jvs.2010.07.044.
Results publication: PubMed 20393508Shigematsu H, Yasuda K, Iwai T, Sasajima T, Ishimaru S, Ohashi Y, Yamaguchi T, Ogihara T, Morishita R. Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia. Gene Ther. 2010 Sep;17(9):1152-61. doi: 10.1038/gt.2010.51. Epub 2010 Apr 15.
Results publication: PubMed 40221835Di X, Liu C, Sun S, Qin J, Guo X, Chen Y, Li X, Zhang H, Liu M, Yang L, Zhao H, Lu S, Huang J, Zhang Y, Li J, Lin X, Yao K, Tang J, Wang J, Gao Z, Wang J, Huang X, Xu S, Liu Y, Han W, Ni L, Ye W, Zheng Y, Chen Y, Liu B. Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial. Mol Ther. 2025 Jul 2;33(7):3423-3433. doi: 10.1016/j.ymthe.2025.04.009. Epub 2025 Apr 11.
Results publication: PubMed 31805256Gu Y, Cui S, Wang Q, Liu C, Jin B, Guo W, Liu C, Chu T, Shu C, Zhang F, Han C, Liu Y. A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia. Mol Ther. 2019 Dec 4;27(12):2158-2165. doi: 10.1016/j.ymthe.2019.10.017. Epub 2019 Oct 31.
Results publication: PubMed 21898720Hahn W, Pyun WB, Kim DS, Yoo WS, Lee SD, Won JH, Shin GJ, Kim JM, Kim S. Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model. J Gene Med. 2011 Oct;13(10):549-55. doi: 10.1002/jgm.1603.
Results publication: PubMed 20668482Pyun WB, Hahn W, Kim DS, Yoo WS, Lee SD, Won JH, Rho BS, Park ZY, Kim JM, Kim S. Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia. Gene Ther. 2010 Dec;17(12):1442-52. doi: 10.1038/gt.2010.101. Epub 2010 Jul 29.
Results publication: PubMed 21372298Zhao J, Wang W, Ha CH, Kim JY, Wong C, Redmond EM, Hamik A, Jain MK, Feng GS, Jin ZG. Endothelial Grb2-associated binder 1 is crucial for postnatal angiogenesis. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1016-23. doi: 10.1161/ATVBAHA.111.224493. Epub 2011 Mar 3.
Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Jingyong Huang contact

Xiang Su contact

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jingyong Huang (+8613600672565, 43737136@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to First Clinically Driven MALE or All-Cause Death (time frame: From randomization through Day 360 (±14 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07827521, which also lists 52 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.