NCT07352800

Safety of Antithrombotic Heparin Proteoglycan Mimetic APAC in Peripheral Arterial Occlusive Disease and Chronic Limb-threatening Ischemia

A Phase 2a Open-label Study to Assess the Safety, Tolerability, and Dosing Regimen of Antithrombotic Heparin Proteoglycan Mimetic APAC in Patients With Peripheral Arterial Occlusive Disease and Chronic Limb-threatening Ischemia Undergoing Endovascular Revascularization

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Aplagon Oy · Industry
• Sex: All
• Age: 85 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to learn if a new medicine (called antiplatelet and anticoagulant \[APAC\]) can help the body to prevent blood clots and whether APAC is safe and well tolerated in patients with blocked or narrowed arteries in their legs (peripheral arterial occlusive disease \[PAOD\]), and in patients with severely restricted poor blood flow to the legs that threatens limb health (chronic limb-threatening ischemia \[CTLI\]). The study also aims to find the best dose of the medicine. The study consists of two parts: Part A will include patients with PAOD and CTLI, Part B will only include patients with CTLI who are having a procedure to restore blood flow in their legs. Both parts will be subdivided into two subgroups (A1 and A2, B1 and B2) which will test different APAC doses and compare single dosing to weekly dosing for 4 weeks. APAC is injected into the blood. The possible treatment response will be compared either to a placebo (a look-alike substance that contains no drug), or to the current standard treatment. Patients will participate in the study for up to 90 or 180 days. During this time, patients will be regularly examined and asked to answer questions concerning their quality of life.

Detailed description

Peripheral arterial occlusive disease is a group of vascular disorders characterized by narrowing and occlusion of peripheral arteries, often resulting in gradual reduction of the blood supply to the limbs. The main pathogenic mechanism of PAOD stems from atherosclerosis, thrombo-inflammation and thrombosis (atherothrombosis). Patients with PAOD are at increased risk of major adverse limb events (MALE, defined as above ankle amputation of the index limb or major reintervention) and major adverse cardiovascular events (MACE). The most severe form of PAOD, CTLI, is characterized by severely decreased blood flow to the lower limbs. This Phase 2a open-label study will evaluate the safety, tolerability, and dosing regimen of the heparin proteoglycan mimetic APAC in patients with PAOD with moderate claudication (Fontaine stage IIa and IIb) and in patients with CLTI (Fontaine stage III and IV) undergoing endovascular revascularization. The study consists of two parts (Part A and Part B), both with two subparts: * in Part A1, a single dose will be administered intravenously (i.v.), * in Part A2, weekly doses will be administered i.v. for 4 weeks, * in Part B1, a single dose will be administered intra-arterially (i.a) periprocedurally, and * in Part B2, the first dose will be administered i.a. periprocedurally, followed by weekly i.v. dosing for 4 weeks. Part A will evaluate APAC in the PAOD/CLTI patient population. The primary objective is to evaluate safety and tolerability of i.v. APAC for single infusion (Part A1) and weekly dosing (Part A2). Secondary objectives include evaluation of the effects of APAC on the clinical status of PAOD, and assessment of pharmacokinetic (PK), pharmacodynamic (PD) and other blood coagulation parameters. In Part A1, patients are randomized (2:1) to APAC and control groups. In Part A2, patients are randomized (2:2:1) to two APAC dose levels and control. In Part A, safety and recommended dose(s) of APAC for Part B are studied. A Safety Review Committee (SRC) will evaluate the Part A1 and Part A2 data after all patients in a group have completed the Day 8 or Day 29 visit, respectively, and decide the use of reserve doses, and recommend the dose(s) for the Part B. Part B will evaluate APAC in CTLI patients undergoing endovascular revascularization. As primary objective, safety of the selected dose(s) and dosing frequency of periprocedural i.a. and weekly i.v. APAC administration will be evaluated. Secondary objectives aim to establish a dosing regimen (single vs. multiple dosing) and preliminary efficacy. Moreover, PK, PD and other blood coagulation parameters, as well as the effects of APAC on MALE and MACE-free survival and quality of life will be assessed as secondary objectives. For both subparts (B1 and B2), patients will be randomized in 2:1 ratio to APAC and control groups. Part B1 with periprocedural dosing can start after the favorable SRC statement from Part A1. All other study parts (Part A1 \[Day 8\], Part A2 \[Day 29\], and Part B1 \[Day 29\]) need to be finalized before the start of Part B2. For all study patients, the duration of screening period is maximum 28 days. Safety and clinical measures will be collected until the end of the follow-up period (Part A1: Day 29, and Parts A2, B1, B2: Day 90). To assess the effects of APAC on clinical outcome and quality of life, study participants will be followed up for 90 days in Part A1 and 180 days in Part A2, Part B1, and Part B2 after the first dose of APAC. The study ends when the patient has completed the Day 90 (Part A1) and Day 180 (Part A2, B1, and B2) telephone survey to assess quality of life.

Conditions

• Peripheral Arterial Occlusive Disease
• Chronic Limb-Threatening Ischemia

Interventions

Type	Name	Description
DRUG	APAC - dose level 0.50 mg/kg,	single i.v. dosing
OTHER	Unfractionated heparin (UFH)	administered as standard of care
DRUG	APAC dose level 1: 0.25 mg/kg,	weekly i.v. dosing for 4 consecutive weeks
OTHER	Vehicle (sterile saline, NaCL 0.9%)	weekly i.v. dosing for 4 consecutive weeks
DRUG	APAC dose level 2: 0.50 mg/kg,	weekly i.v. dosing for 4 consecutive weeks
DRUG	APAC (single periprocedural dose)	Dose is selected based on Part A data, periprocedural dosing.
DRUG	APAC	Dose is selected based on Part A and Part B, periprocedural dosing plus dosing for 4 consecutive weeks.

Timeline

• Start date: 2026-01-29
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2026-01-20
• Last updated: 2026-04-09

Locations

3 sites across 1 country: Finland