Aplagon Doses First Patient in Phase 2a Trial of APAC for Chronic Limb Threatening Ischemia
核心洞察
Aplagon (搜索) has dosed the first patient in its Phase 2a HEALING clinical trial evaluating APAC (搜索), a first-in-class heparin proteoglycan (搜索) mimetic treatment for peripheral arterial occlusive disease (搜索) leading to chronic limb threatening ischemia (搜索).
The study will enroll up to 42 patients across four cohorts in Finland to assess safety and preliminary efficacy of intravenous APAC (搜索), with CLTI (搜索) representing a severe condition with 25% one-year mortality rate.
APAC (搜索) demonstrated dose-dependent antithrombotic effects and good tolerability in a completed Phase 1 trial of 30 healthy volunteers, with the therapy designed to target vascular injury sites and prevent restenosis after revascularization procedures.
Aplagon (搜索), a clinical-stage biotech company, has achieved a significant milestone by dosing the first patient in its Phase 2a HEALING clinical trial of APAC (搜索), a first-in-class treatment for thrombo-inflammatory diseases. The trial focuses on patients with peripheral arterial occlusive disease (搜索) (PAOD (搜索)) leading to chronic limb threatening ischemia (搜索) (CLTI (搜索)).
Trial Design and Patient Population
The single- and repeat-dose study is taking place in Finland and will enroll up to 42 patients across four cohorts. The trial has been designed to provide a preliminary indication of safety and efficacy of APAC (搜索) in CLTI (搜索) patients, both with and without revascularization, while also examining the therapy's effect on thrombo-inflammatory biomarkers (搜索).
CLTI (搜索) represents a severe form of PAOD (搜索) caused by atherosclerosis (搜索)-related thrombo-inflammation, resulting in insufficient blood flow in the affected limb. The condition carries a grave prognosis, with a mortality rate of 25% in the first year and significant risk of limb amputation. The most important risk factors include diabetes and cigarette smoking.
Mechanism of Action and Administration
APAC (搜索) functions as a heparin proteoglycan (搜索) mimetic with antiplatelet and anticoagulant effects. The therapy targets arterial injury sites, providing long-lasting antithrombotic and anti-inflammatory action in situ by mimicking naturally occurring mast cell-derived heparin proteoglycans. The treatment can be administered either locally or intravenously in hospital settings, supporting uptake by vascular surgeons and angiologists.
"APAC (搜索) has been shown to prevent platelet aggregation (搜索) and blood clotting. Previous studies have also shown that it reduces the inflammatory response in tissues damaged by oxygen deprivation during short follow-ups," explained Maarit Venermo, Professor of vascular surgery at Helsinki University Hospital (搜索).
Clinical Development Progress
The Phase 2a trial received FIMEA approval following successful completion of an international Phase 1 clinical trial in 30 healthy participants. The Phase 1 study demonstrated that APAC (搜索) was well tolerated, with dose-dependent and transient systemic antithrombotic effects. An associated PET-imaging clinical trial using 89zirconium-labeled APAC in PAOD (搜索) patients and healthy participants is scheduled to complete in the first half of 2026.
Addressing Unmet Medical Need
Current treatments for PAOD (搜索) do not cure the disease but only alleviate symptoms. While revascularization procedures are often effective, restenosis occurs in approximately one-third of treated arteries after endovascular treatment, even when patients receive antithrombotic medication according to current treatment guidelines. This represents a significant limitation of current endovascular treatment approaches.
"Through these actions, APAC (搜索) enhances the medical treatment of lower limb arterial atherosclerosis (搜索), accelerate the healing of tissue damage caused by ischemia, and prevent restenosis after revascularization procedures, thereby reducing the need for reinterventions," Venermo noted.
Future Development Plans
Aplagon (搜索) is also planning a Phase 2 clinical trial for arteriovenous fistula (AVF) maturation failure in Europe for 2026, following successful completion of its Phase 1 AVF trial. The study demonstrated encouraging early maturation results with no safety concerns.
"We're delighted to have achieved this significant clinical milestone and dosed our first patient in our Phase 2a trial to treat PAOD (搜索)/CLTI (搜索)," said Aki Prihti, CEO at Aplagon (搜索). "Our innovative approach, using a heparin proteoglycan (搜索) mimetic with targeting ability and retention on the vascular injury sites, has potential applications across a broad range of serious vascular diseases caused by thrombo-inflammation."