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.
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.
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.
Parallel
Lower-Extremity Revascularization
Procedure/SurgeryAll 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 Seltoplasmid
GeneticSeltoplasmid 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.
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.
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.
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.
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.
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First Affiliated Hospital of Wenzhou Medical University
Lead sponsor
Beijing Northland Biotech. Co., Ltd.
Collaborator
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