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.
Males aged 45-85 years and postmenopausal females (i.e., no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
Diagnosed with a. PAOD classification Fontaine stage III or IV , b. the total length of the treatment-targeted arterial segment ≥ 5 cm below the knee lesion(s) based on contrast-enhanced computed tomography angiography (CTA)/magnetic resonance angiography (MRA)/digital subtraction angiography (DSA) (Part B1 and B2), c. superficial forefoot wounds without overt infection and bone invasion (WIfI 0-1 and 2 limited to digits and WIfI infection 0-1) allowed, d. undergoing endovascular intervention. (In Part A1, if prescheduled endovascular intervention would take place before the Day 8 study visit, patient is not to be enrolled.)
CTA/MRA/DSA with contrast agent performed within 3 months prior to study enrolment as part of diagnostics of PAOD, with results available in the patient's medical records.
Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg once a day [QD]) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
Any ischemic lesions of the heel and midfoot and lesions (wounds or gangrene) invading bones, joints, or tendons at metatarsophalangeal joints or more proximal sites.
Acute limb-threatening ischemia (e.g., thromboembolic disease).
Medical history of, or an existing aneurysm.
Endovascular revascularization intervention is done from the contralateral side using cross-over access (Part B1 and B2).
Sequential
APAC - dose level 0.50 mg/kg,
Drugsingle i.v. dosing
Unfractionated heparin (UFH)
Other interventionadministered as standard of care
APAC dose level 1: 0.25 mg/kg,
Drugweekly i.v. dosing for 4 consecutive weeks
Vehicle (sterile saline, NaCL 0.9%)
Other interventionweekly i.v. dosing for 4 consecutive weeks
APAC dose level 2: 0.50 mg/kg,
Drugweekly i.v. dosing for 4 consecutive weeks
APAC (single periprocedural dose)
DrugDose is selected based on Part A data, periprocedural dosing.
APAC
DrugDose is selected based on Part A and Part B, periprocedural dosing plus dosing for 4 consecutive weeks.
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Treatment groupsSee each treatment group below.
Primary endpoint - Part A: Occurrence and severity of treatment-emergent adverse events (TEAEs)
Primary endpoint - Part B: Occurrence and severity of TEAEs
Secondary endpoint 1 - Part A: Fontaine classification
No unit of measure
Secondary endpoint 1 - Part A: Wound Ischemia foot Infection (WIfI) scoring
No unit of measure
Secondary endpoint 1 - Part A: Toe-brachial blood pressure index (TBI) and ankle-brachial systolic blood pressure index (ABI)
No unit of measure
Secondary endpoint 1 - Part A2: Maximal walking distance in a treadmill exercise test
Unit of measure: meters
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